technetium-tc-99m-bicisate and Cerebrovascular-Disorders

Brain SPECT studies are used to evaluate the cerebral hemodynamic changes in cerebrovascular diseases and other neuro-psychiatric disorders. I-123 and Tc-99m labeled radiopharmaceuticals widely used for brain perfusion SPECT studies include I-123 IMP, Tc-99m HMPAO, and Tc-99m ECD. I-123 IMP is suitable for the quantitative evaluation of cerebral blood flow, while Tc-99m HMPAO and Tc-99m ECD have problems owing to the non-linearity between cerebral radioactivity and cerebral blood flow. In addition, Tc-99m ECD does not show cerebral blood flow in the subacute phase of cerebral infarct or other conditions. Thus, it is important to consider the characteristics of radiopharmaceuticals and the clinical aspect of brain lesions in the interpretation of brain perfusion SPECT images. In this review, some useful information on brain perfusion SPECT is presented mainly as it relates to the cerebrovascular diseases.

Topics: Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Iofetamine; Mental Disorders; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Brain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimoto's thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of 99mTc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent.. The diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent 99mTc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere--frontal, temporal, parietal and occipital--and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry.. As assessed by visual examination, 99mTc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered.. These results show the high prevalence of brain perfusion abnormalities in euthyroid HT. These abnormalities are similar to those observed in cases of severe Hashimoto's encephalopathy and may suggest a higher than expected involvement of CNS in thyroid autoimmune disease.

Topics: Adult; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Goiter, Nodular; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Statistics as Topic; Thyroiditis, Autoimmune; Tomography, Emission-Computed, Single-Photon

Split-dose injection using technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) and consecutive SPET measurements performed before and after acetazolamide (ACZ) loading was used to estimate the cerebral perfusion reserve. The disadvantage of the split-dose method is that the signal-to-noise ratio (S/N) of ACZ-loaded images is decreased by subtraction of the 1st SPET data (rest) from the 2nd SPET data (ACZ loaded). To improve the S/N of reconstructed images, we implemented an iterative reconstruction algorithm including the term of remaining radioactivity in the brain from the 1st injection. It was expected that this method (the "addition method") would improve the S/N of rest and ACZ images compared with the conventional subtraction method owing to exclusion of the subtraction process. To evaluate the effect of statistical noise, we estimated the percentage coefficient of variation (%COV) as a function of total photon counts (from 1.35 to 86.5 Mcounts/slice) by Monte Carlo simulation with equal-volume split-dose injection. The %COV of the 2nd SPET study was higher than that of the 1st (e.g. 50.3% for the 1st and 80.5% for the 2nd at a total count of 2.70 Mcounts/slice) when using the conventional subtraction method. By contrast, the %COV of the 1st and 2nd SPET studies was almost equivalent (e.g. 43.1% for the 1st and 41.4% for the 2nd at a total count of 2.70 Mcounts/slice) when using the addition method. We also determined the optimal injection dose ratio of the 2nd to the 1st SPET study, which provides the equivalent %COV value between the 1st and 2nd images. With the subtraction method, the optimal injection dose ratio of the 2nd to the 1st SPET study was approximately 2.0, while with the addition method it was approximately 1.0. The absolute value of %COV at the optimal injection dose was about 54% and 43% with the subtraction method and the addition method, respectively. The addition method gave a lower %COV value than the subtraction method even at the optimal injection dose ratio. In a clinical study, the addition method provided better quality images than the subtraction method. The ROI values of rest images estimated by the subtraction method were close to the results obtained with the addition method (ROI(sub)=1.01 ROI(add)-0.312, r=0.999). The ROI values of the ACZ images estimated by the subtraction method also agreed with the results obtained using the addition method, but the correlation was slightly worse (ROI(sub)=1.03 ROI(add)-2.23, r=0.9

Topics: Algorithms; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Computer Simulation; Cysteine; Humans; Image Enhancement; Injections, Intravenous; Organotechnetium Compounds; Quality Control; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Tomography, Emission-Computed, Single-Photon

99mTc ethyl cysteinate dimer (99mTc-ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in patients with acute carbon monoxide (CO) poisoning. Ten patients with acute CO poisoning and no past histories of psychoneurological disorders were enrolled in this study. After oxygen treatment, all of the 10 patients were investigated using 99mTc-ECD brain SPECT and brain computed tomography (CT) scan. Brain CT scan findings were normal in all of the 10 patients. 99mTc-ECD brain SPECT showed the hypoperfusion lesions of the basal ganglia and brain cortex in five and seven patients, respectively. Only three of the 10 patients had normal 99mTc-ECD brain SPECT findings. This study suggests that, in comparison with brain CT scan, 99mTc-ECD brain SPECT is a better tool for the early detection of hypoperfusion brain lesions in acute CO poisoning in patients with normal brain CT findings.

Topics: Adolescent; Adult; Brain; Brain Ischemia; Carbon Monoxide Poisoning; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Organotechnetium Compounds; Radiography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The clinical applicability of dynamic single photon emission tomograpy (SPET) using a dual-head gamma camera equipped with a slip-ring rotational mechanism, referred to as serial SPET, was examined in the present investigation. Serial SPET enables the production of tomographic images for any arbitrary time frame from an arbitrary range of data to 360 degrees. In a pre-clinical evaluation, a correlation between radioactivity concentration and serial SPET counts was evaluated in a phantom with continuous changes in 99mTc concentration. A differential value was obtained from each pair of SPET images; moreover, moving average approximation processing was investigated with respect to the elimination of noise in the data. In 11 and one patient presenting with cerebrovascular disease and meningioma, respectively, changes in SPET counts were evaluated when 99mTc ethyl cysteinate dimer (99mTc-ECD) was continuously administered at a constant rate in the resting state. Furthermore, in six of 11 subjects with cerebrovascular disease, changes occurring in SPET counts were examined by using acetazolamide loading while continuously administering 99mTc-ECD at a constant rate. Consequently, serial SPET enabled the evaluation of changes in radioactivity concentration over time in both the phantom and preliminary clinical studies. Data analysis by differential processing utilizing moving average approximation processing enabled the detection of minor changes in radioactivity concentration. An increase of 15.1+/-5.4% was observed in SPET counts of the unaffected cerebral hemisphere with acetazolamide loading. The response of the affected hemisphere was less prominent. These findings suggest that serial SPET would be an effective technique for the pharmacokinetic analysis of radiopharmaceuticals.

Topics: Acetazolamide; Aged; Brain; Cerebrovascular Disorders; Cysteine; Feasibility Studies; Female; Gamma Cameras; Humans; Male; Meningioma; Middle Aged; Organotechnetium Compounds; Phantoms, Imaging; Quality Control; Radiopharmaceuticals; Rotation; Tomography, Emission-Computed, Single-Photon

We have constructed a three-dimensional stereotaxic ROI template (3DSRT) on anatomically standardised cerebral blood flow (CBF) single-photon emission tomography (SPET) images to objectively estimate regional CBF (rCBF). The 3DSRT is composed of 259 regions of interest (ROIs) in 11 segments (1, superior frontal; 2, middle and inferior frontal; 3, primary sensorimotor; 4, parietal; 5, angular; 6, temporal; 7, occipital; 8, pericallosal; 9, lenticular nucleus; 10, thalamus; 11, hippocampus) on each side. We measured the rCBF values of the 518 ROIs and calculated the area-weighted average (segmental CBF; sCBF) of the 22 segments based on the rCBF in each ROI. We compared vascular reserve before and after revascularisation surgery using sCBF on anatomically standardised resting and acetazolamide (Acz)-challenged CBF SPET images, which were obtained using an equal-volume-split dual-injection single-day protocol [resting and vascular reserve (RVR) method] in 13 patients who had not suffered any major stroke but did have significant cerebrovascular stenosis. Prior to the evaluation, we examined the sCBF values of 16 subjects with various cerebrovascular conditions (8, normal; 3, lacunar infarction; 2, chronic infarction; 2, meningioma; 1, aneurysm) using physiological saline instead of Acz (placebo study) in order to confirm the reproducibility of the RVR method. In the placebo study we observed excellent linearity (y=1.444+0.964x) between the 352 pairs of baseline (x) and post-placebo (y) sCBF values in the 16 subjects, irrespective of the segment location. In all of the 13 patients, estimation of sCBF demonstrated impaired vascular reserve pre-operatively and improved vascular reserve postoperatively. We conclude that the 3DSRT, which could be identically set on the anatomically standardised images obtained at baseline and after Acz injection, allowed objective assessment of the pre- and postoperative vascular reserve, which was not easy with conventional ROI settings. While 3DSRT appeared useful for the evaluation of regional vascular reserve as well as rCBF, further study is necessary to clarify its general clinical value.

Topics: Acetazolamide; Adult; Aged; Aged, 80 and over; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Data Display; Female; Humans; Image Enhancement; Imaging, Three-Dimensional; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Extracorporeal rheopheresis is a safe method to optimize hemorheology. Our aim was to determine whether treatment with extracorporeal rheopheresis in patients with acute ischemic hemispheric stroke improves cerebral perfusion as assessed with serial 99mTc-ethyl-cysteinate-dimer single-photon emission CT (99mTc-ECD SPECT). We also investigated how clinical outcome is associated with treatment and imaging results.. Thirty-three patients (mean age, 64+/-10 years) with acute ischemic hemispheric stroke were included in a prospective, randomized, parallel group pilot study. First treatment with or without extracorporeal rheopheresis took place within 12 hours after the onset of symptoms and was repeated 3 times at intervals of 24 hours. Hemorheological parameters were measured before and after each session. Each patient underwent 99mTc-ECD SPECT immediately before treatment, 6 to 8 hours after treatment, and after 5 days. A semiquantitative SPECT graded scale was used to measure depth and extent of activity deficits and thus to quantify the perfusion deficit.. Seventeen patients were actively treated with extracorporeal rheopheresis, and 16 patients did not receive extracorporeal rheopheresis. After 3 months, no differences were found in the functional or neurological outcome. Despite a rapid, sustained decrease of plasma viscosity and erythrocyte aggregation in the rheopheresis group, there was no significant difference in the SPECT graded scale after therapy between the 2 groups. Patients with early reperfusion (decrease in the SPECT graded scale >25% 6 to 8 hours after therapy compared with the baseline examination) experienced a better functional outcome (Modified Rankin Scale) after 3 months compared with patients without reperfusion (P=0.04).. Since quantitative flow mapping and clinical follow-up did not reveal any differences between patients who were treated with extracorporeal rheopheresis and controls, it appears very unlikely that extracorporeal rheopheresis enhances reperfusion after acute cerebral ischemia.

Topics: Acute Disease; Adult; Aged; Blood Viscosity; Brain Ischemia; Cerebrovascular Disorders; Cysteine; Extracorporeal Circulation; Female; Hemofiltration; Humans; Male; Middle Aged; Organotechnetium Compounds; Pilot Projects; Radiopharmaceuticals; Rheology; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The time-activity curve for the aortic arch obtained from radionuclide angiography (RNA) is handled as an input function parameter according to the method of Matsuda et al., which determines regional cerebral blood flow non-invasively. The data are collected from a frontal view of the thorax captured by RNA by their method, however we encountered a case in which it was difficult to identify aortic arch in the data collection from the frontal view. The precise identification of the aortic arch was implemented when the RNA data were collected from the left anterior oblique view of the thorax. No significant difference was noted in the measured values between the data collection from the frontal view and from the left anterior oblique view. Our method seems to be useful modification of the Patlak plot method.

Topics: Aged; Aorta, Thoracic; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Data Collection; Female; Gamma Cameras; Humans; Male; Middle Aged; Organotechnetium Compounds; Radionuclide Angiography; Radiopharmaceuticals

The aim of this study was to develop a simple, noninvasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ethyl cysteinate dimer (ECD) by a single SPECT scan and single venous sampling.. Using a three-compartment model, we introduced the regional brain fractionation index (BFI), Cb(Ts)/integral of 0-Ts Ca(tau)dtau [Ca(t), arterial input; Cb(t), brain activity]. Regional BFI obtained at the optimum time Ts (min) was converted to rCBF using an exponential function, which was obtained by analyzing the relationship between regional BFI and rCBF (= F) obtained by the standard 133Xe inhalation SPECT method. The integral of the concentration of 99mTc-ECD in arterial blood corrected for physical decay [Ca(t)] in BFI was estimated from a single venous blood sample obtained at the optimum time Tv using the regression line obtained by analyzing the relationship between the integral of Ca(t) and venous sample data. The data come from three groups of patients. The first group of patients (n = 16) underwent a complete 99mTc-ECD BFI study with measurement of Ca(t) and dynamic SPECT scanning, as well as a 133Xe inhalation study to measure rCBF The results were used to analyze the relationship between regional BFI and rCBF (obtained with 133Xe) and to determine the optimum time Ts for obtaining BFI. Data from the second group of patients (n = 15) were used to analyze the relationship between the integral of Ca(t) and venous sample data and to determine the optimum time Tv for one-point venous blood sampling. Finally, the third group of patients (8 patients, 10 studies) was used to validate the current method by comparing the results with 133Xe inhalation SPECT.. Regional BFI obtained at time Ts = 20 min showed good agreement (r = 0.907; a = 0.552, b = 0.962) with rCBF. The venous sample data obtained at time Tv = 6 min showed a good correlation (r = 0.988) with BFI. In comparing rCBF values thus obtained and those obtained by the 133Xe method, we found a good correlation (r = 0.917, slope = 1.01).. The proposed method has three advantages: (a) accurate quantification of rCBF without underestimation in the high flow range, (b) simplicity and noninvasiveness and (c) the ability to use any type of SPECT camera for the study.

Topics: Administration, Inhalation; Adult; Aged; Brain; Brain Chemistry; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Regression Analysis; Reproducibility of Results; Time Factors; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

We sought to study the prognostic value of early 99mtechnetium-ethyl-cysteinate-dimer single-photon emission CT (99mTc-ECD SPECT) for fatal ischemic brain edema in patients with middle cerebral artery (MCA) stroke compared with the prognostic value of CT and of clinical findings.. We prospectively studied 108 patients clinically, with 99mTc-ECD SPECT, and with CT within 6 hours of symptom onset (Scandinavian Stroke Scale <40 points) appropriate to MCA ischemia. The follow-up consisted of Scandinavian Stroke Scale and CT on days 1 and 7, Barthel Index, and Modified Rankin Scale after 3 months. An activity deficit of the complete MCA territory on the SPECT scans and a parenchymal hypoattenuation of the complete MCA territory on CT scans were considered as predictors for a fatal MCA infarction due to mass effect and midbrain herniation.. In 11 of 108 patients (10%), the MCA infarction was the cause of death. The sensitivity of SPECT for fatal outcome was 82% in both visual and semiquantitative analyses, while specificity was 98% and 99%, respectively. The sensitivity and specificity of baseline CT were 36% and 100%, respectively; the sensitivity and specificity of clinical findings (Scandinavian Stroke Scale, depressed level of consciousness, gaze deviation) varied from 36% to 73% and from 45% to 88%, respectively. In a multivariate logistic regression model, only SPECT findings were found to be independent predictors of malignant MCA infarction/death.. We were able to identify patients with fatal MCA infarction with high accuracy by using 99mTc-ECD SPECT within 6 hours of stroke onset. This technique offers great potential to select stroke patients for specific therapies, eg, decompressive hemicraniectomy, soon after onset of symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Edema; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Prognosis; Prospective Studies; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

To evaluate noninvasive regional cerebral blood flow (CBF) measurements using technetium-99m-L, L-ethyl cysteinate dimer (99mTc-ECD), radionuclide angiography, resting- and acetazolamide-activating-SPECT studies were performed during about one hour. Forty-four cases with diagnosis of cerebral ischemic disorders were studied. For 36 cases (Group "Acz"), radionuclide angiography was performed immediately after intravenous bolus injection of 300 MBq of 99mTc-ECD, followed by the consecutive SPECT studies. In the midst of the first SPECT study, acetazolamide was administered. Just after the completion of the first SPECT study, another 300 MBq of 99mTc-ECD was added and the second SPECT study was started. For the remaining 8 cases (Group "Placebo"), physiological saline was administered instead of acetazolamide. Quantitative flow-mapping image was calculated from the qualitative SPECT image by the application of Patlak plot graphical analysis and Lassen's correction. Group "Placebo" showed no increase of mean CBF (mCBF) between the resting- and the placebo-challenged-SPECT image (2nd mCBF/1st mCBF; 98 +/- 5%). Group "Acz" showed 124 +/- 15% increase of mCBF under acetazolamide activation. By use of these quantitative flow-mapping images, acetazolamide-activated CBF increase was recognized clearly and easily. This noninvasive method is easy to perform and may be helpful to measure cerebral perfusion changes in the acetazolamide test.

Topics: Acetazolamide; Adult; Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radionuclide Angiography; Regional Blood Flow; Tomography, Emission-Computed, Single-Photon

A multicenter study was performed in seven European centers comparing 99mTc-bicisate with 133Xe as a means of evaluating bicisate as a tracer of CBF distribution in humans. The same type of single photon emission computed tomography (SPECT) instrument (Tomomatic) was used in all centers. A total of 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between the results of the two methods was noted in 98 cases, but not in the remaining 7, all belonging to the stroke group. These seven all suffered from a subacute stroke (11-23 days after onset), and the disagreement in all cases consisted of bicisate showing low count rate in the area of the infarct and Xe a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute stroke cases does bicisate not follow CBF, as it fails to show reperfusion hyperemia. This suggests the usefulness of bicisate in stroke cases, particularly in the subacute phase, where other SPECT methods often present difficulties due to reflow masking the size and the severity of the lesion.

Topics: Aged; Brain Diseases; Brain Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic Disease; Cysteine; Female; Humans; Hyperemia; Male; Organotechnetium Compounds; Reference Values; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

Single photon emission computed tomography (SPECT) using 99mTc-bicisate and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) was compared in 25 patients suffering cerebral ischemia during the subacute phase (7-14 days) of stroke. Patients were classified as cortical strokes (15) and subcortical strokes (10) according to clinical and CT data. Images were analyzed by five independent blinded observers. Then, using a cross-matching method between normal and abnormal brain areas, we evaluated the sensitivity and specificity for 99mTc-bicisate and [123I]IMP and inter- and intraobserver reproducibility. A semiquantitative analysis was performed to compare abnormal hypoactive areas versus the corresponding contralateral areas for 99mTc-bicisate and [123I]IMP in the two patient groups. There was no significant difference for sensitivity and specificity between 99mTc-bicisate and [123I]IMP. Matching was approximately 90% in the two groups. The kappa-concordance index was satisfactory and slightly better for 99mTc-bicisate (0.485) than for [123I]IMP (0.435). Level of hypoactivity in the abnormal areas was significantly higher for 99mTc-bicisate (p < 0.03, n = 25) than for [123I]IMP, especially for cortical strokes. This comparative study demonstrates that 99mTc-bicisate is a very useful tracer for the detection of focal cerebral ischemia by SPECT during the subacute phase of stroke.

Topics: Adult; Aged; Aged, 80 and over; Amphetamines; Brain; Cerebrovascular Disorders; Cysteine; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Reference Values; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Ischemia; Cerebrovascular Disorders; Cysteine; Female; Humans; Hyperemia; Male; Middle Aged; Organotechnetium Compounds; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

A phase 3 clinical study of a newly developed brain perfusion agent, 99mTc-L,L-ethyl cysteinate dimer (99mTc-ECD), was performed in 521 cases of cerebrovascular diseases and impairment of brain function to evaluate the safety, effectiveness and usefulness of the agent as a multi-center study involving 35 institutions in Japan. Out of 510 cases evaluated for the clinical usefulness, valuable information for clinical diagnosis was obtained in 486 cases (95.3%), and 444 cases (87.1%) were judged as "extremely useful" or "useful". Although the positive ratio of abnormalities detected by the agent was as same as that of 99mTc-hexamethylpropyleneamine oxime (99mTc-HM-PAO), the abnormal regions detected by the agent had tendency to be larger in size and to have higher contrast than those detected by 99mTc-HM-PAO. It is concluded that 99mTc-ECD is a safe and useful radiopharmaceutical as a brain perfusion agent for the diagnosis of cerebrovascular diseases and impairment of brain function.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A phase 2 clinical study of a newly developed brain perfusion agent, 99mTc-ECD, was performed in 166 cases of cerebrovascular diseases and impairment of brain function to evaluate effectiveness, usefulness, optimum dose and optimum timing of imaging as a multi-center study involving 10 institutions in Japan. All cases were judged as no problems on safety and any side effects due to the administration of the compound were not observed. Out of 163 cases evaluated for the clinical usefulness, valuable information for clinical diagnosis was obtained in 160 cases (98.3%), and 154 cases (94.5%) were judged as "extremely useful" or "useful". Although SPECT imaging was possible from 5 min after injection, images obtained between 60 and 90 min after injection showed relatively better image quality in many cases. Regarding standard administration dose, 400 to 800 MBq were considered to be appropriate. 99mTc-ECD is considered to be a promising radiopharmaceutical as a brain perfusion agent.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

We created a new normal database of elderly individuals (Tsukuba-NDB) for easy Z-score Imaging System (eZIS), a statistical imaging analysis software, comprised of 44 healthy individuals aged 75 to 89 years. The Tsukuba-NDB was compared with a conventional NDB (Musashi-NDB) using Statistical Parametric Mapping (SPM8), eZIS analysis, mean images, standard deviation (SD) images, SD values, specific volume of interest analysis (SVA). Furthermore, the association of the mean cerebral blood flow (mCBF) with various clinical indicators was statistically analyzed. A group comparison using SPM8 indicated that the t-value of the Tsukuba-NDB was lower in the frontoparietal region but tended to be higher in the bilateral temporal lobes and the base of the brain than that of the Musashi-NDB. The results of eZIS analysis by Musashi-NDB in 48 subjects indicated the presence of mild decreases in cerebral blood flow in the bilateral frontoparietal lobes of 9 subjects, precuneus and posterior cingulate gyrus of 5 subjects, lingual gyrus of 4 subjects, and near the left frontal gyrus, temporal lobe, superior temporal gyrus, and lenticular nucleus of 12 subjects. The mean images showed that there were no visual differences between both NDBs. The SD images intensities and SD values were lower in Tsukuba-NDB. Clinical case comparison and visual evaluation demonstrated that the sites of decrease in blood flow were more clearly indicated by the Tsukuba-NDB. Furthermore, mCBF was 40.87 ± 0.52 ml/100 g/min (mean ± SE), and tended to decrease with age. The tendency was stronger in male subjects than female subjects. Among various clinical indicators, the platelet count was statistically significantly correlated with CBF. In conclusion, our results suggest that Tsukuba-NDB, which is incorporated into a statistical imaging analysis software, eZIS, is sensitive to changes in cerebral blood flow caused by Cranial nerve disease, dementia and cerebrovascular accidents, and can provide precise diagnosis of these brain diseases in the rapidly aging Japanese population.

Topics: Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Databases, Factual; Female; Humans; Image Processing, Computer-Assisted; Male; Neurodegenerative Diseases; Organotechnetium Compounds; Radiopharmaceuticals; Software; Tomography, Emission-Computed, Single-Photon

Topics: Cerebrovascular Disorders; Cysteine; Female; Hallucinations; Humans; Magnetic Resonance Angiography; Middle Aged; Organotechnetium Compounds; Tomography Scanners, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Vasoconstriction

The Patlak plot method of measuring cerebral blood flow (CBF) to improve the repeatability and quantitative capability, by using technetium-99m ethyl cysteinate dimer (99mTc-ECD). We calculated CBF and then statistically analyzed its relationships with various hematological and biochemical parameters. There were significant statistical correlations between these clinical parameters and the measured values of mean CBF (mCBF), also between these biochemical parameters and post-acetazolamide (p-ACZ) mCBF, in terms of estimated glomerular filtration rate (eGFR), serum albumin level, red blood cell count, blood urea nitrogen level, and random blood glucose level. In addition, statistically significant correlations were found between these parameters and increased mCBF. Another significant correlation was found between cerebrovascular reserve capacity (CVR) and platelet count. Values of p-ACZ mCBF and CVR were lower in a group with HbA(1C) >7% and high blood glucose levels than in healthy subjects. In addition, values of resting mCBF and p-ACZ mCBF were lower in a group with kidney dysfunction (eGFR <30 ml/min/1.73 m2) than in subjects with normal renal function or mild dysfunction. A multiple linear regression analysis showed a correlation between resting mCBF value and eGFR. Therefore, there were correlations between CBF and the levels of these parameters of diabetes or chronic kidney disease. These results suggest that our Patlak plot modified method may be a potentially useful tool for analyzing the relationships between CBF and underlying diseases and/or the pathophysiology of CBF dysfunction. The post-ACZ ECD Patlak resting and vascular reserve (p-ACZ ECD Patlak RVR) test provides a way of detecting minor changes in CBF, which is difficult to reveal by only resting Patlak plot method, in patients with lifestyle diseases such as diabetes or chronic kidney disease. In addition, we believe that a new modified method contribute to predict risk of cerebral vascular disorders along with clinical parameters.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Biomarkers; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Child, Preschool; Cysteine; Female; Humans; Infant; Life Style; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Sex Factors; Tomography, Emission-Computed, Single-Photon; Young Adult

Intravascular lymphomatosis (IVL) is known to affect both hemispheres of the brain and manifests clinically as seizures or dementia. To our knowledge, there have been no cases in which acute hemispheric dysfunction is manifested in IVL. We present a 54-year-old man who showed steroid responsive acute hemispheric dysfunction. A technetium 99m-ethyl cysteinate dimer single-photon emission computed tomographic scan of the brain revealed hypoperfusion in the right hemisphere. The bone marrow biopsy specimen confirmed malignant lymphoid cells in vessels, which suggested IVL. Our case signifies the diversity of clinical manifestations in IVL.

Topics: Antineoplastic Agents; Biopsy; Bone Marrow Examination; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Cysteine; Fatal Outcome; Humans; Lymphoma; Magnetic Resonance Angiography; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Shock, Septic; Steroids; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vascular Neoplasms

Augmentation of the cerebral blood supply to correct cerebral hemodynamic insufficiency by extracranial-intracranial bypass may be an appropriate method to reduce the risk of ischemic stroke. Eighty-five patients with ischemic symptoms, decreased regional cerebral blood flow, and decreased regional cerebrovascular reactivity were recruited for surgery. The post-bypass mean regional blood flow increased by 35.8% compared to the pre-bypass value (p<0.001). Only minor re-establishment of vasculature after anastomosis was detected in three of four patients with middle cerebral artery stenosis, which suggests that there are fewer benefits of bypass surgery in this situation. Cerebral infarction occurred immediately post-operation in one patient who was predisposed to stroke due to a bilateral carotid occlusion. Hyperperfusion injury was infrequent in this series; only one patient developed intracerebral hemorrhage three weeks after the bypass. One ischemic and one hemorrhagic stroke occurred during the 90 months following surgery.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Angiography, Digital Subtraction; Cerebral Angiography; Cerebral Revascularization; Cerebrovascular Disorders; Cysteine; Female; Hemodynamics; Humans; Male; Middle Aged; Organotechnetium Compounds; Postoperative Complications; Predictive Value of Tests; Regional Blood Flow; Retrospective Studies; Taiwan; Tomography, X-Ray Computed; Young Adult

Extracranial-intracranial (EC-IC) bypass surgery remains an important treatment alternative for patients with occlusive cerebrovascular disease. The aim of the present study was to use perfusion CT and CT angiography (CTA) to evaluate cerebral hemodynamics and bypass patency in patients with occlusive cerebrovascular disease before and after EC-IC bypass surgery.. Ten patients underwent perfusion CT and CTA before and after bypass surgery. Preoperative and postoperative digital subtraction angiography served as the diagnostic gold standard. An artery bypass was established from the superficial temporal artery to a cortical branch of the middle cerebral artery. Perfusion CT scanning was performed at the level of the basal ganglia. Color-coded perfusion maps of cerebral blood volume, cerebral blood flow, and time to peak were calculated.. Preoperative perfusion CT showed significant prolonged time to peak and reduced cerebral blood flow of the affected hemisphere. Postoperative neurological deterioration did not develop in any patient. Computed tomography angiography provided adequate evaluation of the anastomoses as well as the course and caliber of the bypass and confirmed bypass patency in all patients. Postoperative perfusion CT showed improved cerebral hemodynamics with a return to nearly normal perfusion parameters.. Computed tomography angiography is a noninvasive and reliable tool for evaluating patients with EC-IC bypass. Perfusion CT allows monitoring of hemodynamic changes after bypass surgery. The combination of both modalities enables noninvasive anatomical and functional analysis of superficial temporal artery-middle cerebral artery anastomoses using a single CT protocol. Hemodynamic evaluation of patients with occlusive cerebrovascular disease before and after surgery may improve the prediction of outcome and may help identify patients in whom a bypass procedure can be performed.

Topics: Anastomosis, Surgical; Angiography, Digital Subtraction; Cerebral Angiography; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Follow-Up Studies; Humans; Monitoring, Intraoperative; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome; Vascular Grafting

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N'-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03-0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method.

Topics: Cerebrovascular Circulation; Cerebrovascular Disorders; Chemistry Techniques, Analytical; Cysteine; Cystine; Drug Stability; Humans; Organotechnetium Compounds; Quality Control; Radionuclide Imaging; Radiopharmaceuticals; Reagent Kits, Diagnostic; Sulfur

This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion.. Analysis of data derived from two separate data banks.. 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25).. Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by (99 m)Tc-ECD SPECT. Statistical analysis was done through logistic regression.. MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group.. In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

Topics: Adolescent; Adult; Aged; Celiac Disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Depressive Disorder, Major; Female; Goiter; Hashimoto Disease; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Diabetes mellitus increases the risk of ischemic stroke. The aim of this study was to investigate the correlation between fasting plasma glucose (FPG) and changes in regional cerebral perfusion (CP) in subjects with DM.. CP was assessed in 24 subjects (mean age 44+/-2.5 years) with type 1 diabetes mellitus by single photon emission computed tomography.. Analysis of CP during elevated FPG (224+/-24 mg/dL) showed 3 or more deficits in 42% of the subjects. A positive relationship between the number of CP deficits and FPG was observed (P<0.01), but not with age, sex, body mass index, or duration of diabetes mellitus. Regional deficits were reduced (P<0.001) with improvement in FPG (119+/-5 mg/dL). This reduction remained significant after adjustment for age, sex, and body mass index. Plasma levels of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, established markers of endothelial dysfunction, were significantly decreased with lower FPG. Furthermore, thiobarbituric acid reactive substance plasma levels, an index of oxidative stress, were also reduced (P<0.01).. The present study demonstrates that changes in FPG are associated with functional changes in regional CP. Hyperglycemia-induced endothelial dysfunction may be implicated in the impaired regional CP of diabetic subjects.

Topics: Adult; Biomarkers; Blood Glucose; Causality; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Diabetes Complications; Endothelial Cells; Female; Humans; Hyperglycemia; Intercellular Adhesion Molecule-1; Male; Middle Aged; Organotechnetium Compounds; Oxidative Stress; P-Selectin; Predictive Value of Tests; Prognosis; Radiopharmaceuticals; Thiobarbituric Acid Reactive Substances; Tomography, Emission-Computed, Single-Photon; Vascular Cell Adhesion Molecule-1

Topics: Alexander Disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Medulla Oblongata; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Depressive symptoms are common in Alzheimer's disease (AD) and contribute to clinical morbidity. Previous studies have suggested that hypoperfusion in the prefrontal cortex and anterior cingulate gyrus are involved in the pathophysiology of depression. Using the easy Z-score imaging system (eZIS), we investigated the relationship between depressive symptoms and prefrontal hypoperfusion in AD. Tc-99m-ethyl cysteinate dimer (Tc-99m-ECD)-single photon emission tomography (SPECT) and Neuropsychiatric Inventory (NPI) were performed in forty-four patients diagnosed as having Dementia of Alzheimer's type (DAT) with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). These patients were divided into the depressive group (D group: n=26) and non-depressive group (ND group: n=18) using NPI depression items. All data from SPECT images were analyzed using eZIS software. Scores in four regions were determined by Z-values; these regions consisted of each side of the prefrontal cortex and anterior cingulate gyrus. The mean scores between the D group and ND group were compared. The mean scores of the left prefrontal cortex in the D group were significantly higher (p<0.0125) than those in the ND group. There were no significant differences in the scores of the right prefrontal cortex and the bilateral anterior cingulate gyrus between these two groups (Mann-Whitney U-test). These findings suggest that hypoperfusion in the left prefrontal area contributes to the expression of depressive symptoms in patients with DAT.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Depressive Disorder; Female; Functional Laterality; Gyrus Cinguli; Humans; Male; Organotechnetium Compounds; Predictive Value of Tests; Prefrontal Cortex; Tomography, Emission-Computed, Single-Photon

To investigate the regional cerebral blood flow (rCBF) changes in patients with idiopathic generalized epilepsy (IGE), we compared brain single photon emission computed tomography (SPECT) images of drug naïve IGE patients with those of age/sex matched healthy volunteers.. Brain interictal 99mTc-ethylcysteinate dimer SPECT was performed in 21 patients with IGE (M/F = 10/11, 21.3 +/- 2.7 years) and 21 normal controls. The seizure types were generalized tonic-clonic seizure in 14 patients and myoclonic seizures with rare generalized tonic-clonic seizures in seven. Differences of rCBF between an IGE group and a normal control group were examined by the statistical parametric mapping (SPM) of brain SPECT images using independent t test.. The SPM analysis showed that the rCBF of the IGE patients was significantly reduced in the anterior and posterior cingulate gyri, bilateral anterior nuclei and right dorsolateral nucleus of the thalamus, right superior colliculus of the midbrain, and the cerebellum at the level of uncorrected p < 0.005. In the small volume correction analysis for the thalamus and brainstem, the rCBF was also significantly decreased in the same brain regions at the level of FDR corrected p < 0.05. No brain regions of the IGE patients had increased rCBF.. Our study demonstrates that the interictal rCBF in drug naive IGE patients is reduced in the cingulate gyrus, thalamus, brainstem and cerebellum. This result suggests that dysfunctions in these brain regions are associated with IGE.

Topics: Adolescent; Adult; Brain; Brain Mapping; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Down-Regulation; Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Humans; Male; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

The Patlak plot method is widely used in general clinical practice to calculate mean cerebral blood flow (mCBF) because it does not require arterial blood sampling and the procedure used is relatively simple. However, it has been pointed out that the calculation is affected by operator subjectivity and experience, and reproducibility is poor when the operator changes. The Patlak plot method consists of the following three procedures: (1) a region of interest (ROI) in the normal cerebral hemisphere is chosen to obtain the time-activity curve; (2) an ROI in the aortic arch is determined to obtain the time-activity curve; and (3) graphic analysis of the two time-activity curves is performed, and mCBF is determined from the slope of the graph. In this study, we automated all three of the above procedures, enabling analysis that is not affected by operator subjectivity or experience. Considering the verification result shown below: (1) automation of an ROI setup of a cerebral hemisphere and an aortic arch was possible in all examples; (2) the point of graphic analysis was set in the error range of 1% - 2% of straight line domains; (3) in comparison with the conventional method in 55 cases, the mean of absolute percentage error was 3.1+/-2.5%; (4) in 17 cases that did not accept a right-and-left difference in SPECT, the mean of absolute percentage error of right and left mCBF was 1.3+/-0.9%. It was thought that the processing algorithm was appropriate. Moreover, it was thought that the technique of graphic analysis proposed for this study served as an aid to dissolution of the "ambiguity" of the Patlak plot method.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Gamma Cameras; Humans; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Software; Tomography, Emission-Computed, Single-Photon

To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLT showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [P < 0.05 by Student's t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit.

Topics: Adolescent; Adult; Brain; Brain Mapping; Cataplexy; Caudate Nucleus; Cerebrovascular Disorders; Cysteine; Data Interpretation, Statistical; Female; Humans; Hypothalamus; Image Processing, Computer-Assisted; Male; Middle Aged; Narcolepsy; Organotechnetium Compounds; Polysomnography; Radiopharmaceuticals; Sleep; Tomography, Emission-Computed, Single-Photon

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 32 female patients with primary Sjögren's syndrome (PSS) showing definite neuropsychiatric symptoms/signs and normal brain magnetic resonance imaging (MRI) findings. It demonstrated hypoperfusion brain lesions in 18 (56.3%) of the patients, most frequently in the parietal lobes, and appears to be a sensitive tool for this clinical application.

Topics: Adult; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Mental Disorders; Middle Aged; Nervous System Diseases; Organotechnetium Compounds; Radiopharmaceuticals; Sjogren's Syndrome; Tomography, Emission-Computed, Single-Photon

Topics: Acetazolamide; Adolescent; Aged; Aged, 80 and over; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Cysteine; Data Display; Female; Humans; Image Enhancement; Imaging, Three-Dimensional; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

We previously developed an alternative method for estimating the brain perfusion index (BPI) using technetium-99m compounds and spectral analysis (SA) for quantification of cerebral blood flow (CBF). In this study, we investigated the reproducibility of the BPI values obtained by SA (BPIS) using a double injection of technetium-99m ethyl cysteinate dimer without any intervention, and compared it with that of the BPI values obtained by graphical analysis (BPIG). The BPIS values in the first (x) and second sessions (y) correlated closely (y=0.921x+0.036; r=0.962; n=64; s.e.e.=0.058 min-1). Although the BPIG values in the first (x) and second sessions (y) also correlated (y=0.942x+0.040; r=0.916; n=64; s.e.e.=0.061 min-1), the correlation coefficient for BPIS was significantly higher than that for BPIG. The reproducibility was dependent on the injection dose ratio of the second session to the first (R). The difference in BPI between the first and second sessions tended to be smaller when 1.5

Topics: Aged; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon

Previous functional neuroimaging studies performed during transient global amnesia (TGA) have not answered the central question regarding the etiology of TGA, namely: whether the observed hypoperfusion in the mesial temporal lobe structures reflects a primarily ischemic process or whether it represents a secondary phenomenon resulting from locally decreased metabolism. The authors performed Tc 99-m-bicisate brain single photon-emission computed tomography (SPECT) scanning in a 66-year-old man during an episode of TGA, 24 hours after the episode and 3 months after the episode. To the authors' knowledge, this is the only reported study in which a follow-up SPECT scan was performed within 24 hours. The initial study showed bilateral mesial temporal lobe hypoperfusion that partially resolved after 24 hours and returned to normal at 3 months. Resolution of the SPECT scan abnormalities correlated well with resolution of the memory loss. These findings agree with previously reported SPECT, positron-emission tomography (PET), and diffusion magnetic resonance imaging (MRI) studies that indicate the mesial temporal lobe structures as the major site of pathology in TGA. The authors suggest that a process causing decreased local metabolism, such as cortical spreading depression, constitutes the primary pathophysiologic mechanism in this case.

Topics: Aged; Amnesia, Transient Global; Brain Ischemia; Cerebrovascular Disorders; Cortical Spreading Depression; Cysteine; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Organotechnetium Compounds; Radiopharmaceuticals; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The aim of this study was to develop a new method for quantifying regional cerebral blood flow (rCBF) with technetium-99m ethyl cysteinate dimer (ECD) and single-photon emission tomography (SPET). Employing a three-compartment model, we introduced a parameter, regional brain fractionation index (BFI), that reflects rCBF values and is obtained by a single SPET scan at optimum time T (min) after tracer injection and the integral of arterial input. By analysing the dynamic SPET and arterial blood sampling data of 15 subjects, including the results of acetazolamide challenges, with the graphical plot method, optimum time T was determined to be approximately 20 min post injection. Regional BFI values of each subject were calculated from the single SPET data at 20 min and arterial input. The relationship between the values of regional BFI and rCBF obtained by xenon-133 inhalation SPET was analysed by approximation with an exponential function, resulting in good agreement (r = 0.907). In the present method, rCBF values were determined from regional BFI values by using the inverse exponential function as a non-linear regression curve. To validate the method, we applied it to six other subjects, in whom acetazolamide challenges were also performed. In comparing rCBF values thus obtained and those obtained by 133Xe inhalation SPET, we found a good correlation (r = 0.901) with an inclination approximating 1 (= 1.02) and without underestimation of rCBF in the high-flow range. Since the present method does not require dynamic planar imaging or dynamic SPET scanning, it can be applied to any type of SPET scanner and is useful in clinical SPET studies.

Topics: Brain; Case-Control Studies; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

This present study was carried out to investigate whether stabilization of Tc-99m-HMPAO with methylene blue (MB) or cobalt chloride (CC) causes a sensible improvement in image quality and how cerebral to noncerebral activity ratios compare with those of Tc-99m-ECD.. 30 minutes after preparation 400-600 MBq unstabilized Tc-99m-HMPAO (N = 35 patients), Tc-99m-HMPAO added with MB (N = 24 patients), added with CC (N = 30 patients) or Tc-99m-ECD (N = 28 patients) were injected. Radiochemical stability was measured in vitro with three chromatographical methods. Image quality was assessed quantitatively using two ratios, one of them determined by count densities of brain/scalp (Os), the other one by count densities of brain/nose (QN). In addition, image quality (0 = bad, 3 = excellent) and background activity (0 = high, 3 = no) were visually assessed by three independent observers.. In contrast to unstabilized Tc-99m-HMPAO the integrity of the complexes of MB-Tc-99m-HMPAO, CC-Tc-99m-HMPAO and Tc-99m-ECD decreased only by a few percent during a period of 2 hours after reconstitution (66.8 +/- 9.9 vs. 93.0 +/- 2.5, 91.8 +/- 1.9 and 96.9 +/- 1.4%, p < 0.001). Qs and Qn (m.v. +/- SD) differed significantly between studies using unstabilized Tc-99m-HMPAO (3.0 +/- 0.4 and 2.1 +/- 0.3), MB-Tc-99m-HMPAO (3.4 +/- 0.4 and 2.3 +/- 0.3), CC-Tc-99m-HMPAO (3.6 +/- 0.6 and 2.6 +/- 0.4) and those using Tc-99m-ECD (4.3 +/- 0.7 and 4.8 +/- 1.4, p < 0.05 and < 0.001). Stabilization with CC or MB resulted in significant higher scoring of image quality and lower scoring of background activity in comparison to that of unstabilized Tc-99m-HMPAO, without reaching the scores obtained with Tc-99m-ECD.. It is concluded that stabilization of Tc-99m-HMPAO with MB or CC definitely improves image quality in rCBF-SPECT, without reaching that of Tc-99m-ECD. Improvement of image quality results from the reduction of the amount of decomposition products that contribute to considerable extracerebral activity.

Topics: Adult; Aged; Aged, 80 and over; Brain; Cerebrovascular Disorders; Cobalt; Cysteine; Depression; Drug Stability; Female; Humans; Male; Methylene Blue; Middle Aged; Neurodegenerative Diseases; Organotechnetium Compounds; Radiopharmaceuticals; Scalp; Sensitivity and Specificity; Sleep Apnea Syndromes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Because 99mTc-HMPAO and 99mTc-ECD are both used for SPECT imaging of cerebral blood flow, the question arises whether there are any differences in their respective regional cerebral distribution. For that purpose, visual and semiquantitative comparisons between 99mTc-HMPAO and 99mTc-ECD studies were performed.. Seventeen patients (4 women; 13 men; age 45-89 yr; mean age 71 yr) with various neurological diseases, except acute/subacute stroke, were investigated twice with 99mTc-HMPAO and 99mTc-ECD using a triple-headed rotating SPECT camera. After image reorientation, the two studies were evaluated visually. Seventy regions of interest (ROIs) were drawn manually and the same set of ROIs was applied in both studies. Regional indices (RI) normalized to individual brain values were calculated and first compared between two random patient groups. Second, for all patients, RI for 70 and later for 27 regions (gained after summing values of corresponding regions in different brain slices) were compared by using a paired Student's t-test applying Bonferroni's correction.. Visual evaluation demonstrated relatively high 99mTc-ECD uptake in occipital and comparatively low uptake in mediotemporal regions. Calculation of RI revealed significantly higher values in the right cerebellum, brainstem, mediotemporal regions, right basal ganglia and the thalamus in the 99mTc-HMPAO SPECT studies and higher values in the occipital, supratemporal/inferior parietal and parietal cortex in the 99mTc-ECD SPECT studies, respectively.. Significant differences in regional tracer distribution between 99mTc-HMPAO and 99mTc-ECD could be detected, probably caused by different tracer kinetics. The results indicate that direct comparisons of studies performed with 99mTc-HMPAO and 99mTc-ECD are not possible and the use of either tracer can be favorable in different clinical questions.

Topics: Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Epilepsy; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) at pre- and post Diamox test using split-dose 99mTc-ECD and SPECT. By employing a microsphere model, integral of input function was calculated by the one-point venous sampling method previously reported. The study was performed on 5 subjects with cerebrovascular diseases. A split dose of 99mTc-ECD was injected pre- and post Diamox injection, and rCBF was measured by two SPECT scans and single venous samples, respectively. Mean CBF obtained by the present method was 0.47 +/- 0.07 ml/g/min at the control state, and 0.63 +/- 0.12 ml/g/min loaded with Diamox (mean % increase; 35%), showing good agreement with those obtained by the 133Xe-inhalation method. Since the present method does not require arterial blood sampling, dynamic data acquisition and dose corrections, it is simple, less invasive and useful in clinical SPECT studies.

Topics: Acetazolamide; Adult; Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Aged; Brain; Cerebrovascular Disorders; Child, Preschool; Cysteine; Dementia; Epilepsy; Humans; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Discrepancies have been reported between the findings of Tc-99m HMPAO and Tc-99m ECD brain perfusion SPECT imaging. This study investigated the discrepancies in the accumulation of these tracers using dynamic SPECT to detect the super early phase of distribution. Thirteen patients with luxury perfusion or high flow states were studied with both dynamic and standard SPECT using Tc-99m HMPAO and Tc-99m ECD within 1-3 days. Standard SPECT showed discrepancies in 6 of 13 patients. Patients with meningioma and cerebral thrombosis had increased accumulation of Tc-99m HMPAO and decreased uptake of Tc-99m ECD. Patients with arteriovenous malformation, subarachnoid hemorrhage, and cavernous angioma had decreased accumulation of both tracers, but to different degrees. Dynamic SPECT showed increased or normal accumulation (i.e., essentially no discrepancy) in the first few minutes. However, Tc-99m HMPAO had a longer retention time than Tc-99m ECD in the ensuing 5-10 minutes. Dynamic SPECT revealed a similar accumulation pattern but different washout rates for the two tracers. Tc-99m HMPAO might be a more suitable tracer to detect high flow states or luxury perfusion because the findings on standard SPECT were more in agreement with those of dynamic SPECT using this tracer.

Topics: Adult; Aged; Brain; Brain Diseases; Brain Neoplasms; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Hyperemia; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A new method for quantitative measurement of regional cerebral blood flow (rCBF) before and after acetazolamide (Diamox) administration was developed using 99mTc labeled ethyl cysteinate dimer (ECD) and consecutive SPECT with continuous arterial blood sampling. Moreover, the correction was proposed for underestimation of rCBF due to the inherent low first pass extraction of ECD in high blood flow regions. The rCBF values obtained by the microsphere model in 5 patients correlated well with those obtained by 133Xe gas inhalation method. The slope of the regression line, however, was 0.576 due to the underestimation of high CBF values. The reproducibility of two resting rCBF obtained by the microsphere model proposed here was confirmed in another 5 patients with the mean values of 41.8 +/- 5.6 ml/100 g/min and 38.9 +/- 5.3 ml/100 g/min for the 1st and 2nd measurement, respectively. The correction of rCBF obtained with ECD and the proposed microsphere model was performed using the permeability-surface area product model described by Crone. In 14 patients with cerebrovascular diseases, the corrected rCBFs correlated well with those by 133Xe gas inhalation method with the improvement of the slope of regression line (0.427 to 0.865), although the correlation coefficient did not change significantly (0.697 to 0.699). The results indicated that the proposed correction method could reflect precisely the increase in rCBF elicited after Diamox administration, so that the cerebral perfusion reserve could be evaluated more exactly than the methods which have ever been utilized in the routine clinical measurements.

Topics: Acetazolamide; Administration, Inhalation; Adult; Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Linear Models; Male; Microspheres; Middle Aged; Organotechnetium Compounds; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

A new index of cerebral blood flow (brain uptake ratio, BUR) using 99mTc-ECD was developed and evaluated in 66 patients (132 cerebral hemispheres). BUR was calculated from brain count in anterior planar image (60-80 sec after injection of 99mTc-ECD) divided by the summation of the count of aortic arch during first transit of radionuclide. BUR correlated well with brain perfusion index (BPI) obtained with Patlak plot method (r = 0.960, p < 0.001). In conclusion, BUR is useful as a simple and non-invasive index reflecting cerebral blood flow.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood-Brain Barrier; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Microspheres; Middle Aged; Organotechnetium Compounds; Perfusion; Radionuclide Imaging

Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution.. Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed.. Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area.. In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.

Topics: Blood-Brain Barrier; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Oxygen Consumption; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

We compared the acetazolamide challenge test using 99mTc-ECD SPECT and 123I-IMP SPECT images in patients with chronic occlusive cerebrovascular disease. We also evaluated the usefulness of linearization correction for acetazolamide challenge test of 99mTc-ECD SPECT.. Twenty patients with unilateral chronic occlusive cerebrovascular disease (10 patients had middle cerebral arterial lesion and 10 had internal carotid lesion) were included in the study. Split-dose (a dose fractioning was 1:2), and sequential SPECT technique was used for 99mTc-ECD SPECT studies while only acetazolamide challenge test studies for 123I-IMP SPECT were performed. Permeability surface area product model (PS model) and back-diffusion model (Lassen's correction) were used for linearization correction of acetazolamide challenge with 99mTc-ECD SPECT.. Six of 16 patients with reduced vasodilatory capacity in 123I-IMP SPECT were underestimated by 99mTc-ECD SPECT acetazolamide challenge test. Relative ECD uptake normalized by cerebellar uptake compared with IMP uptake showed a nonlinear relationship, indicating relatively less uptake in high flow range. The underestimations of limited vasodilatory capacity observed in 99mTc-ECD SPECT without linearization correction was modified by linearization algorithm. However, the effect of correction based on PS model was superior than that of Lassen's correction. The corrected 99mTc-ECD uptake ratio, based on PS model, and IMP uptake ratio demonstrated a better linear relationship than that of Lassen's correction.. Technetium-99m ECD SPECT corrected based on the PS model is a better method of linearization for evaluating cerebrovascular reserve using acetazolamide challenge.

Topics: Acetazolamide; Aged; Aged, 80 and over; Amphetamines; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic Disease; Cysteine; Female; Humans; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Vasodilation

We propose a new method to quantify regional cerebral blood flow (rCBF) with continuous infusion of 99mTc-ethyl cysteinate dimer (ECD) and dynamic SPECT.. Thirteen subjects were studied. Seven subjects had SPECT and PET studies, and the other six subjects were involved in the measurement of blood clearance of 99mTc-ECD. During constant infusion of 99mTc-ECD (740 MBq) over 10 min, dynamic SPECT scans were obtained every 1 min by means of a triple-head rotating SPECT camera. Intermittent arterial blood sampling with octanol extraction was performed every 1 min to estimate the arterial input function. Influx constant (Ku) obtained by Gjedde-Patlak graphical plot method was compared with rCBF measured by PET using 15O CO2 steady state method. In order to simplify the procedure, arterial input function in each subject was estimated by calibration of the arterial blood sampled at the end of the scan to the standard arterial input function estimated from the blood clearance rate in six subjects.. Ku was linearly correlated with rCBF (Ku = 0.09 + 0.62 rCBF, r = 0.85, p < 0.05). Ku calculated with the estimated input function (Ku') and rCBF also demonstrated a linear relationship (Ku' = 0.05 + 0.65 rCBF, r = 0.84, p < 0.05).. The proposed method with one-point arterial sampling is a simple, clinically feasible tool for quantitative measurement of rCBF with 99mTc-ECD.

Topics: Adult; Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

We measured regional cerebral blood flow before and after acetazolamide administration using a serial noninvasive method with 99mTc-ECD developed by Matsuda and Takeuchi et al., and compared the accuracy of measured values with those obtained by the conventional 123I-IMP ARG method. When the regional cerebral blood flow was measured for 80 brain regions in 5 subjects without scatter correction, a differential of 0.5 +/- 8.4% was obtained between values measured before and after physiological saline administration as a placebo. A differential of -0.2 +/- 12.6% was obtained when the same regions were measured with scatter correction. These findings indicated that placebo administration did not affect measured values, regardless of whether scatter correction was performed. When 64 regions in 4 subjects at rest were measured on two successive days, a differential of -1.1 +/- 9.0% was obtained between the values measured on the two days. A differential of -4.0 +/- 11.7% was obtained for the same regions following acetazolamide administration. These findings showed that measurements were reproducible both when subjects were at rest and when they were administered acetazolamide. The above two methods were used for measurement of 80 brain regions in the same 5 subjects for comparison. Measurements of subjects at rest and with acetazolamide administration were performed on separate days. The regression line y = 0.99x + 1.47, r = 0.80, was obtained for the subjects at rest, and y = 0.86x + 7.76, with r = 0.76, for the subjects following acetazolamide administration. These findings demonstrated a good correlation between the values obtained using the two methods. The values obtained using the method of Matsuda and Takeuchi et al., before and after acetazolamide administration were thus consistent with those reported previously using the conventional method, and the former method proved to be both simple and reliable.

Topics: Acetazolamide; Aged; Aged, 80 and over; Amphetamines; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon

A one-day protocol with a double injection of 99mTc-ECD was introduced for the assessment of cerebral perfusion reserve with acetazolamide (ACZ). The purpose of this study was to investigate the feasibility and effectiveness of this protocol.. Thirty subjects were given double injections of 99mTc-ECD (first dose 370 MBq; second dose 740 MBq) for consecutive brain perfusion studies. Serial dynamic SPECT scans (1 min x 50 frames) were performed with the first set of SPECT data obtained by totaling the data for the frames taken between 5 and 20 min, and the second by subtracting the decay and dose-corrected initial SPECT data from the sum of the data obtained between 35 and 50 min. To evaluate the feasibility and effectiveness of the procedure, 23 of the 30 subjects were injected with ACZ 14 min after the first dose. To evaluate the reproducibility, seven subjects were not given the ACZ. The washout rate (WR) was calculated for three stages (WR1 = from 6 to 14 min, WR2 = from 20 to 28 min, and WR3 = from 36 to 44 min). Regional count increase (percent increase) and the percent count difference between normal and affected side (percent difference) were also calculated.. Values for WR1, WR2 and WR3 did not show significant differences among the stages (WR1 = -1.43% +/- 6.09%, WR2 = -0.65% +/- 6.57%, and WR3 = -1.60% +/- 4.28%; F-value = 0.33, p-value = 0.72). Reproducibility was excellent (second SPECT = 0.964 x first SPECT; r = 0.997). Mean count increase after ACZ was 21.7%. In patients with unilateral cerebrovascular disease, the percent increase after ACZ loading was significantly greater on the normal side (26.6% +/- 13.0%) than on the affected side (19.3% +/- 13.2%) (p < 0.01), resulting in a significant increase in percent difference (control: 14.3% +/- 10.7%, ACZ: 19.2% +/- 11.5%; p < 0.01).. ECD washout was minimal during the first 50 min after injection and was not affected by ACZ, which supports the feasibility of this protocol. The simple procedure and short acquisition time of this method renders it clinically useful for measuring cerebral perfusion reserve.

Topics: Acetazolamide; Adult; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Vasodilator Agents

Topics: Amphetamines; Brain; Cerebrovascular Disorders; Cysteine; Humans; Iodine Radioisotopes; Iofetamine; Organotechnetium Compounds; Time Factors; Tomography, Emission-Computed, Single-Photon

To evaluate the cerebral pharmacokinetics of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated "luxury perfusion" in subacute stroke, ictal hyperperfusion in epilepsy and post-decompressive hyperemia in head trauma. All 7 patients showed a hyperactive area on SPECT studies using 99mTc-HM-PAO. 99mTc-ECD static image demonstrated a hyperactive area in both epilepsy and head trauma, and a hypoactive area in "luxury perfusion." On the dynamic SPECT of 99mTc-ECD in both epilepsy and head trauma, brain distribution of the tracer was determined within 2 min. postinjection and remained stable for up to 1 hour; however, "luxury perfusion" area showed a change from initial hyperactivity to late hypoactivity with the passage of time. The time activity curve in "luxury perfusion" area demonstrated a steep decrease of counts/pixel for up to 4-5 minutes postinjection, and a moderate decrease in the following phase. The early wash-out mechanism of 99mTc-ECD from "luxury perfusion" area can be described by a biexponential function including an initial steep decrease representing the rapid loss of the lipophilic complexes which were not metabolized in injured brain tissue.

Topics: Acute Disease; Adult; Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

The brain distribution of 99mTc-ECD versus 123I-IMP was compared in patients with subacute stroke in order to compare diagnostic accuracy.. A total of 25 patients with subacute stroke underwent early and delayed SPECT imaging with 99mTc-ECD and 123I-IMP. Washout of 99mTc-ECD was calculated and a differential percentage of activity (DPA) of ischemic versus normal zones was assessed. Images were analyzed twice by five independent observers.. Technetium-99m-ECD clearance was 12.5% from the whole brain during early imaging. Ischemic parietal zones had higher clearance than normal parietal zones. Technetium-99m-ECD images showed larger differences between abnormal and normal brain activity than 123I-IMP images. Detection accuracy was slightly, but not significantly, higher for 99mTc-ECD and 123I-IMP (sensitivity: 73.8% as 66.6%; specificity: 81.7% as 81.6%). Reproducibility among observers was similar for 99mTc-ECD and early 123I-IMP.. Technetium-99m-ECD demonstrates high diagnostic accuracy during subacute stroke, similar to 123I-IMP, but with more intense, better delineation of the perfusion defects.

Topics: Adult; Aged; Aged, 80 and over; Amphetamines; Brain; Cerebrovascular Disorders; Cysteine; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Models, Structural; Organotechnetium Compounds; Sensitivity and Specificity; Time Factors; Tomography, Emission-Computed, Single-Photon

This report describes a comparative study between technetium-99m ethyl cysteinate dimer (ECD) and 99mTc-hexamethylpropylene amine oxime (HMPAO) in five neurological patients. The conversion kinetics of the tracers in the blood from forms capable of diffusion across the blood-brain barrier to non-diffusible forms were studied by arterial sampling and rapid octanol extraction. We observed that HMPAO has a faster conversion rate in the blood but that the fraction of the injected dose available for brain extraction is higher than in the case of ECD. Regional brain concentrations of the tracers were measured with single-photon emission tomography (SPET) 35 min and 60 min after the injection and remained stable within this interval. On the basis of the measurements of the arterial input and of SPET brain concentrations of the tracers, the regional steady-state influx constants (Ki in ml/min/g) were determined for several brain regions. In the grey matter the Ki values were (mean +/- SD) 0.32 +/- 0.03 and 0.35 +/- 0.04 for HMPAO and ECD, respectively; in the white matter the values were 0.23 +/- 0.01 and 0.23 +/- 0.02, respectively. The Ki values of the two tracers in corresponding regions were closely correlated (P < 0.001). The correspondence of the Ki values of ECD and HMPAO demonstrates that ECD can also be considered a tracer that may be used for quantitative measurements of brain perfusion.

Topics: Aged; Alzheimer Disease; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Organotechnetium Compounds; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.

Topics: Adult; Aged; Brain; Capillary Permeability; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Dementia; Female; Humans; Male; Middle Aged; Models, Cardiovascular; Organotechnetium Compounds; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

To evaluate the cerebral distribution of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated postischemic reperfusion and acetazolamide (Diamox) activation test in stroke patients. The postischemic reperfusion was studied in 10 patients who showed a postischemic hyperperfusion area on other single photon emission computed tomography (SPECT) studies using N-isopropyl-rho-[123I]iodoamphetamine ([123I]IMP), 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO), or 133Xe. 99mTc-ECD SPECT demonstrated a hyperactive area in one case, an isoactive area in four, and a hypoactive area in five. Correlations with CT findings revealed hyperactive areas without any abnormality, isoactive areas with perifocal rim, perifocal edema, or diffuse cerebral edema, and hypoactive areas with an infarct core. The Diamox activation test was studied in eight other patients with atherothrombotic stroke, and a limitation in vasodilative capacity was classified into three grades: Gr. 0 (none to minimal), Gr. I (mild), and Gr. II (moderate). [123I]IMP SPECT showed Gr. II and limitation in all eight cases. However, 99mTc-ECD showed Gr. II in three cases and Gr. I in five, and 99mTc-HMPAO revealed Gr. II in two cases, Gr. I in three, and Gr. 0 in three. We suggest that a lack of retention of 99mTc-ECD in a postischemic reperfusion area indicates the severity of the initial brain damage. Although the limitation in vasodilative capacity under Diamox-activated conditions was underestimated using 99mTc-labeled CBF tracers as compared with [123I]IMP, a retention of 99mTc-ECD in the unaffected area with an increased CBF under Diamox activation could be relatively superior to 99mTc-HMPAO.

Topics: Acetazolamide; Adult; Aged; Brain Ischemia; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Reperfusion; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The regional brain uptake of 99mTc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl ester (99mTc-bicisate) measured by single photon emission computed tomography (SPECT) was compared with the regional CBF and CMRO2 measured by positron emission tomography in patients with cerebrovascular disease. Nine patients with the diagnosis of cerebral ischemic disorders (n = 7) or cerebral hemorrhage (n = 2) were studied. 99mTc-Bicisate brain uptake correlated with CBF and CMRO2. However, 99mTc-bicisate uptake did not reflect CBF in the single lesion showing luxury perfusion, which seemed to resemble a CMRO2 image. Though quantitative analysis showed the nonlinear correspondence of 99mTc-bicisate brain uptake with CBF and CMRO2, this correspondence could be corrected into a more linear relationship using a correction factor. 99mTc-Bicisate washout from the brain had no correlation to CBF and CMRO2. This diffuse decreasing washout rate was approximately 15% during the first hour after injection. By using the lipophilic fraction of arterial blood and a linearized correction of 99mTc-bicisate SPECT images, the feasibility of obtaining a factor-related CBF and CMRO2 was suggested from our data. These results suggested that 99mTc-bicisate had good characteristics for routine clinical use with SPECT to display the brain function in patients with neurological disorders.

Topics: Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Oxygen; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Brain perfusion SPECT imaging using Tc-99m ethyl cysteinate dimer (ECD) was carried out in 12 patients with chronic cerebrovascular disease. The sensitivity of lesion detection and lesion-to-normal tissue contrast was compared with those of I-123 IMP and Tc-99m HMPAO. Eight patients underwent all three studies and the remaining four patients had Tc-99m ECD and I-123 IMP scans. The sensitivity of lesion detection and lesion contrast was analyzed quantitatively using an asymmetric index determined by the equation: 100 x [right - left[/(right + left). In the cerebral cortex, cerebellum, and white matter, I-123 IMP showed higher lesion sensitivity than Tc-99m ECD and Tc-99m HMPAO. In the striatum and thalamus, Tc-99m ECD and I-123 IMP showed higher lesion sensitivity than Tc-99m HMPAO. I-123 IMP showed the highest lesion contrast in cerebral cortex and cerebellum, whereas Tc-99m ECD showed the highest contrast in thalamus and striatum. In all regions, Tc-99m ECD showed higher lesion contrast than Tc-99m HMPAO. These results suggest regional variation in the sensitivity of lesion detection and lesion contrast of Tc-99m ECD compared to I-123 IMP, and the superiority of Tc-99m ECD to Tc-99m HMPAO.

Topics: Adult; Amphetamines; Cerebellum; Cerebral Cortex; Cerebrovascular Disorders; Cysteine; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Oximes; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Thalamus; Tomography, Emission-Computed, Single-Photon

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.

Topics: Adult; Aged; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Reference Values; Regression Analysis; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

Technetium-99m ethyl cysteinate dimer (ECD) has recently developed for SPECT imaging in assessment of cerebral perfusion. We evaluated the arterial blood clearance and the regional brain uptake of Tc-99m ECD compared with the regional CBF measured by PET in patients with cerebrovascular disease. Nine patients with diagnosis of cerebral ischemic disorders (N = 7) and cerebral hemorrhage (N = 2) were studied. PET study was performed with HEADTOME IV by O-15 steady state inhalation method. Immediately after the PET study, 555-740 MBq (5-20 mCi) of Tc-99m ECD was injected intravenously. After injection arterial blood sampling was performed sequentially, and we separated lipophilic fraction from whole blood using ethyl acetate in two cases. The SPECT imaging with Tc-99m ECD (ECD-SPECT) was started 5 min (first imaging) and 60 min (second imaging) after the administration using a high resolution ring type SPECT system (HEADTOME II). Several ROIs were placed on practically the same anatomical location on both SPECT and PET images. Clearance of the tracer in arterial whole blood and lipophilic fraction was rapid. Concerning to the distribution pattern of ECD-SPECT images there was no differences between the 1st imaging and the 2nd imaging, although about 15% of diffuse decrease of Tc-99m ECD uptake was shown in the 2nd images. The brain distribution of ECD-SPECT was comparable to the pattern of CBF image by PET. The regional relative counts of ECD-SPECT corresponded closely to the CBF value by PET, but it was no linear correlation between brain uptake of ECD-SPECT and PET-CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

99mTc-ECD SPECT was performed in 19 patients with cerebrovascular disease, and location, extent, and severity of the lesions on 99mTc-ECD SPECT were compared with those on 123I-IMP SPECT. The initial brain uptake was 5.5 +/- 0.7% of the injected dose at 10 minutes after injection, 5.3 +/- 1.3% at 90 minutes, and clearance from the brain is slow. The distribution in the brain was changed, especially washout from the thalamus was slower than that from other regions. The count ratio of perfusion defect to normal area (D/N) on 99mTc-ECD SPECT was unchanged over the time, and had no significant differences from that on 123I-IMP SPECT. 99mTc-ECD SPECT was superior in detection of the lesion in the basal ganglia, and showed the images with superior spatial resolution due to physical characteristics of 99mTc. However, mild ischemic lesion and peri-infarct area was not clearly visualized, while 123I-IMP SPECT could demonstrate these lesions with better contrast.

Topics: Aged; Aged, 80 and over; Amphetamines; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Female; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon