technetium-tc-99m-bicisate and Brain-Ischemia

To analyze the retention process of technetium-99m ethyl cysteinate dimer (99mTc-ECD) in normal and ischemic lesions, we developed a super rapid dynamic SPECT system based on the CERASPECT (DSI, Inc., Waltham, MA, USA). The system made it possible to take a SPECT series every 2 seconds. Each SPECT series contains a maximum of 16 slices (6.6 mm slice interval) in a matrix size of 32 x 32. The sensitivity of this system is 175 kcps/MBq/ml/cm slice thickness, and resolution is 12 mm FWHM at the center of a 20 cm(phi) water phantom. Using the super rapid SPECT system, the kinetic behavior of the 99mTc-ECD during retention in normal and ischemic lesions was analyzed. Twenty patients with ischemic lesions that were clearly demonstrated by 133Xe-rCBF (regional cerebral blood flow) SPECT but unclear on static 99mTc-ECD SPECT were examined. For the dynamic SPECT, 700 MBq of 99mTc-ECD was injected intravenously, and dynamic SPECT data were acquired every 2 seconds during a 90-second period. The serial dynamic SPECT and time-activity curves at some lesions with reduced rCBF and at the contralateral normal brain were analyzed. These dynamic SPECT data were compared with conventional static 99mTc-ECD SPECT and quantitative 133Xe-rCBF SPECT. All of mildly or moderately reduced rCBF lesions on the 133Xe-rCBF SPECT were recognized as low activity regions only at the early phase (during about 2-20 sec or less), with the lesions then gradually vanishing. These lesions were not recognized on the conventional static SPECT taken after the dynamic study. The time-activity curve at the reduced rCBF lesion was lower than that of contralateral normal brain at the early phase, and overtook the activity in the normal region with a gradual increase. The early phase images of 99mTc-ECD SPECT within 20 seconds by the super rapid dynamic SPECT were very useful to the same extent as the 133Xe-rCBF SPECT for detecting mild or moderate ischemic lesions. This study suggests that esterase activity, participating in the ECD retention mechanism, may be tolerable to mild or moderate ischemia. This tolerance may be the main cause of the nonlinear relationship between ECD accumulation and cerebral blood flow.

Topics: Brain; Brain Ischemia; Cysteine; Humans; Image Enhancement; Metabolic Clearance Rate; Organotechnetium Compounds; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Xenon Radioisotopes

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 aim of the present study was to test the hypothesis that perfusion single-photon emission computed tomography (SPECT), carried out in addition to transmission computed tomography (TCT), improves the predictive value of brain imaging within the therapeutically relevant time window after acute cerebral ischemia.. Using TCT and [(99m)Tc]ethyl cysteinate dimer (ECD)-SPECT within 6 hours after symptom onset, we examined 108 patients (44 women, 64 men; mean age 65+/-13 years) with acute ischemic stroke attributed to the territory of the middle cerebral artery (MCA). In each case, 3 experts prospectively evaluated the early SPECT and TCT images. We correlated these ratings with follow-up TCT findings for the final infarction as well as with clinical outcome (Scandinavian Stroke Scale, Barthel Index, Modified Rankin Scale) after 30 and 90 days.. Severe activity deficits on SPECT, not caused by local atrophy on TCT, were the best predictors (positive predictive value [PPV ]94%, 95% CI 89% to 99%; negative predictive value [NPV] 90%, 95% CI 78% to 100%; P<0.001) for evolving cerebral infarction. Complete MCA infarctions were predicted with significantly higher accuracy with early SPECT (area under receiver operating characteristic curve [AUC] index 0.91) compared with early TCT (AUC index 0.77) and clinical parameters (AUC index 0.73, P<0.05). Logistic regression analysis revealed 1 independent predictor for completed MCA territory infarction: SPECT activity deficits in the corresponding areas (PPV 88%, 95% CI 65% to 100%; NPV 96%, 95% CI 92% to 100%; P<0.001). Furthermore, death after stroke was optimally predicted by [(99m)Tc]ECD-SPECT. Clinical outcome up to 90 days after the stroke event best correlated with the degree of activity deficits in early SPECT (r=0.53, P<0.001).. [(99m)Tc]ECD brain perfusion SPECT that completes TCT definitely improves the predictive value of brain imaging after acute cerebral ischemia. Thus, the combined imaging of brain edema and of cerebral perfusion early after stroke is recommended for clinical use.

Topics: Acute Disease; Aged; Brain Infarction; Brain Ischemia; Cysteine; Disease Progression; False Positive Reactions; Female; Follow-Up Studies; Forecasting; Humans; Male; Middle Cerebral Artery; Organotechnetium Compounds; Perfusion; Prospective Studies; Radiopharmaceuticals; Stroke; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

It is unclear from recent clinical trials whether thrombolytic agents are capable of facilitating reperfusion and metabolic recovery over time or whether a beneficial effect is counteracted by an increase in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment on metabolic recovery after reperfusion and clinical outcome.. Patients were prospectively studied with (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD-SPECT) before treatment with recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo (n=26) 6 to 8 hours after treatment and at 7+/-1 days. Activity deficits were graded, compared between the treatment groups, and correlated with clinical outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic brain tissue was defined as a 25% decrease on the SPECT graded scale.. Patients with metabolic recovery (n=28) had a better chance of being functionally unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5, 95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36+/-38 versus 167+/-162 mL), regardless of whether metabolic recovery was observed within 6 to 8 hours of treatment or at 7 days. None of the 28 patients with metabolic recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without recovery (P=0.016). Treatment did not affect the incidence of brain tissue metabolic recovery.. Brain tissue metabolic recovery after ischemic stroke was associated with a beneficial effect on clinical outcome and was not facilitated by treatment with 0.9 mg of intravenous rTPA.

Topics: Aged; Brain; Brain Ischemia; Cysteine; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Reperfusion Injury; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

The aim of this study was to investigate the efficacy of pre- and posttreatment 99mTc-ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography (SPECT) for predicting the ischemic outcome of embolic middle cerebral artery occlusion after treatment with local intraarterial thrombolysis. The authors examined 28 patients with a moderately ischemic area (ratio of affected regional activity to cerebellar activity (A/C ratio) of 0.4 to 0.7) determined using pretreatment SPECT, and with complete recanalization within 6 hours. Posttreatment dynamic and static SPECT studies were performed immediately after thrombolysis. The extent of the affected area outlined on pretreatment SPECT was used for the posttreatment SPECT images, and A/C ratios were calculated. The relative retention ratio of 99mTc-ECD in the affected area was also analyzed using posttreatment dynamic SPECT. Fourteen patients either without infarction or with small subcortical and basal ganglial infarction, 11 patients with medium or large cortical infarction, and 3 patients with hemorrhage were identified by follow-up computed tomography. Ischemic outcome correlated with the relative retention ratio of 99mTc-ECD more closely than either the pre- or posttreatment A/C ratios. In particular, a threshold value for the development of hemorrhage was distinct only in the relative retention ratio of 99mTc-ECD. Pretreatment 99mTc-ECD SPECT did not always predict the occurrence of hemorrhagic transformation, whereas dynamic 99mTc-ECD SPECT performed immediately after thrombolysis allowed clear identification of patients at risk for hemorrhagic transformation.

Topics: Adult; Aged; Brain Ischemia; Cysteine; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Infarction, Middle Cerebral Artery; Injections, Intra-Arterial; Intracranial Embolism; Male; Middle Aged; Organotechnetium Compounds; Predictive Value of Tests; Radiopharmaceuticals; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

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

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

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

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

Cerebral amyloid angiopathy (CAA) is known to be an important cause of spontaneous cortical-subcortical intracranial hemorrhage in normotensive older persons. CAA can also manifest as leukoencephalopathy, brain atrophy, and ischemia secondary to hypoperfusion. Our goal was to verify cerebral hypoperfusion in patients with CAA using (99m)Tc-ethylcysteinate dimer ((99m)Tc-ECD) brain perfusion SPECT.. A total of 11 patients (5 men and 6 women; age range, 58-78 y; mean age +/- SD, 70.0 +/- 7.0 y) with clinically and radiologically established probable CAA who underwent (99m)Tc-ECD SPECT were included. (99m)Tc-ECD SPECT scans were also obtained from 13 age-matched healthy control subjects (7 men and 6 women; age range, 60-79 y; mean age +/- SD, 66.7 +/- 6.4 y) for comparison. The relative regional cerebral blood flow values obtained for patients and controls were compared using software.. Compared with controls, patients with probable CAA showed hypoperfusion in the inferior parietal lobule of both parietal lobes (Brodmann area [BA] 40), middle temporal gyrus of the left temporal lobe (BA 39), postcentral gyrus of the right parietal lobe, superior temporal gyrus of the right temporal lobe (BA 22), superior temporal gyrus of the right frontal lobe (BA 10), inferior temporal gyrus of the left temporal lobe (BA 20), and both caudate bodies (P < 0.0001, t = 4.65).. Patients with probable CAA had significantly decreased cerebral perfusion and may be at risk for leukoencephalopathy, atrophy, and ischemia.

Topics: Aged; Brain; Brain Ischemia; Case-Control Studies; Cerebral Amyloid Angiopathy; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Perfusion Imaging; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

We present a case of subacute middle cerebral artery infarct, which demonstrates restricted diffusion on MRI and reperfusion hyperemia in the posterior half of the lesion on angiography. Tc-99m ethyl cysteinate dimer (ECD) SPECT obtained shortly after the MRI failed to demonstrate perfusion defects in the regions demonstrating reperfusion hyperemia on angiography, underestimating the true size of the infarct. Crossed cerebellar diaschisis is, however, present. SPECT studies obtained over the following weeks demonstrated gradual enlargement of the lesion to approximate the MRI signal changes over a 19-day period. The case presented demonstrates retention of ECD in the infarcted brain. Several studies have demonstrated that Tc-99m ECD uptake is dependent on preserved brain tissue function because tracer retention requires enzymatic esterase activity, rather than the passive, nonenergy dependent trapping of Tc-99m hexamethylpropyleneamine oxime. Hence, infarcted areas undergoing reperfusion hyperemia are unlikely to demonstrate ECD uptake. This report illustrates that MRI diffusion weighted imaging may be more accurate in demonstrating the full extent of reperfused infarcts earlier than Tc-99m ECD SPECT. SPECT in this case failed to demonstrate reduced uptake in reperfused regions of the infarct. Also, crossed cerebellar diaschisis may serve as an early marker of extensive neuronal dysfunction.

Topics: Adult; Brain Ischemia; Cysteine; Diagnostic Errors; Diffusion Magnetic Resonance Imaging; False Negative Reactions; Female; Humans; Hyperemia; Organotechnetium Compounds; Radiopharmaceuticals; Reperfusion Injury; Severity of Illness Index; Stroke; Tomography, Emission-Computed, Single-Photon

To explore the role of single-photon emission CT (SPECT) in initial diagnostic evaluation of patients with mild traumatic brain injury (MTBI) and to identify subgroups in which it may serve as a useful diagnostic tool.. Patients with MTBI seen during a 14-month period were prospectively included in this study. All patients had a CT of head within 12 hours of injury and SPECT by using technetium Tc99m ethyl cysteinate dimer (Tc99m-ECD) within 72 hours of injury. Both SPECT and CT findings were compared with clinical features such as posttraumatic amnesia (PTA), postconcussion syndrome (PCS), and loss of consciousness (LOC).. Ninety-two patients with MTBI underwent SPECT in the study period. There were 28 children and 64 adults, with male-to-female ratio of 4.5 to 1. CT findings were abnormal in 31 (34%) and SPECT in 58 (63%). The most common abnormality was hypoperfusion in the frontal lobe(s) in adults and the temporal lobe in children. A significantly higher number of perfusion abnormalities were seen in patients with PTA (P = .03), LOC (P = .02), and PCS (P = .01) than in patients without these symptoms. Compared to CT, SPECT had a much higher sensitivity for detecting an organic basis in these subgroup, of patients (P < .05).. Tc99m-ECD SPECT can be used as a complementary technique to CT in initial evaluation of patients with MTBI. It is particularly useful in patients having PCS, LOC, or PTA with normal CT scan.

Topics: Adolescent; Adult; Aged; Brain; Brain Concussion; Brain Ischemia; Child; Child, Preschool; Cysteine; Female; Glasgow Coma Scale; Humans; Infant; Male; Middle Aged; Organotechnetium Compounds; Post-Concussion Syndrome; Prognosis; Prospective Studies; Regional Blood Flow; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

When performed soon after stroke onset, single-photon emission computed tomography (SPFCT) with hexamethylpropylenamine oxime or Tc 99m L,L-ethyl cysteinate dimer (ECD) has significant added predictive value compared to neurological scores. With ECD SPECT, the degree of tracer uptake reduction predicts neurological recovery, and using a 40% threshold to characterize irreversibly damaged tissue (IDT), significant correlations have been observed. However, correlations between this uptake threshold and tissue outcomes have not been assessed. The purpose of this study was to validate the 40% ECD uptake threshold for the probabilistic mapping of IDT using an automatic, voxel-based approach.. In 10 acute stroke patients, the authors first compared early ECD SPECT and late coregistered magnetic resonance imaging (MRI) data and assessed for IDT and "tissue at risk" (i.e., tissue with ECD uptake below and above 40%) the percentage of voxels ultimately infarcted and noninfarcted on late brain MRI. They then assessed the correlations between the volumes of brain tissue compartments and subsequent neurological recovery. Finally, to assess whether visual SPECT analysis is reliable compared to the more complex voxel-based approach, the authors compared the predictive value of the 2 methods for neurological recovery.. The majority of IDT voxels (average = 84%), defined by ECD uptake < 40%, evolved toward infarction, and 51.8% to 100% of at-risk voxels (average = 89%) escaped infarction. The extent of IDT correlated significantly with neurological recovery (P = .0009). There was good agreement between visual and voxel-based analyses (P = .0004).. The results support the validity of the ECD uptake thresholds chosen, suggesting that ECD uptake can reflect neuronal viability and that ECD SPECT can be useful for the early detection of potentially salvageable tissue and irreversible damage. These preliminary results encourage the use of this method in a clinical setting for fast decision making in choosing acute therapy.

Topics: Acute Disease; Aged; Aged, 80 and over; Brain; Brain Ischemia; Cysteine; Female; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Stroke; Tomography, Emission-Computed, Single-Photon

Technetium-99m hexamethylpropylene amine oxime (HMPAO) and (99m)Tc- N, N"-1,2-ethylene diylbis- l-cysteine diethyl ester dihydrochloride (ECD) yield significantly different images of cerebral perfusion owing to their particular pharmacokinetics. The aim of this study was to assess the topography, extension and statistical significance of these differences in Alzheimer's disease (AD). Sixty-four patients with mild to moderate AD were retrospectively selected by two European centres. Two series of patients, including 32 studied with (99m)Tc-HMPAO single-photon emission tomography (SPET) and 32 studied with (99m)Tc-ECD SPET, were matched for sex, age (+/-3 years) and severity of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE) (+/-2 points), following a case-control procedure. SPET data were processed using SPM99 software (uncorrected height threshold: P=0.001). (99m)Tc-ECD SPET gave significantly higher uptake ratio values than (99m)Tc-HMPAO SPET in several symmetrical clusters, including the right and left occipital cuneus, the left occipital and parietal precuneus, and the left superior and middle temporal gyri. (99m)Tc-HMPAO SPET gave significantly higher uptake ratio values than ECD in two smaller clusters, including the hippocampus in both hemispheres. In AD, relative brain uptake of (99m)Tc-HMPAO and (99m)Tc-ECD is different in several brain regions, some of which are typically involved in AD, such as the precuneus and the hippocampus. These differences confirm the need for specific normal databases, but their impact on routine SPET reports in AD is not known and deserves an ad hoc investigation.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Brain Ischemia; Case-Control Studies; Cysteine; Female; Humans; Male; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Exametazime

99mTc-ECD SPECT is valuable for the evaluation of cell viability and function. The purpose of the present study was to evaluate the significance of 99mTc-ECD brain SPECT in ischemic stroke. We compared 99mTc-ECD brain SPECT with perfusion and diffusion weighted images (PWI, DWI). Ten patients with acute and early subacute ischemic stroke were included in this prospective study. T2-weighted images (T2WI), DWI, PWI and 99mTc-ECD SPECT were obtained during both the acute/early subacute and late subacute stages. In the case of PWI, time to peak (TTP) and regional cerebral blood volume (rCBV) maps were obtained. The rCBV map and 99mTc-ECD SPECT images were compared in 8 lesions using DeltaAI. The asymmetry index (AI) was calculated as (Ci - Cc) X 200 / (Ci + Cc); where Ci is the mean number of pixel counts of an ipsilateral lesion and Cc is the mean number of pixel counts of the normal contralateral hemisphere. DeltaAI was defined as AIacute - AIsubacute in the ischemic core and periphery. PWI and 99mTc-ECD SPECT detected new lesions of the hyperacute stage or of evolving stroke more accurately than T2WI and DWI. 99mTc-ECD SPECT was able to localize the infarct core and peri-infarct ischemia in all lesions in both the acute and the subacute stages. DeltaAI was higher in the rCBV map than in the 99mTc-ECD SPECT images in the ischemic core (p = 0.063) and in the periphery (p = 0.091). In the 99mTc-ECD SPECT images, DeltaAI was higher in the ischemic core than in the periphery (p = 0.028). During the subacute stage, 99mTc-ECD SPECT detected all the lesions without the pseudonormalization seen in the MR images of 5/11 lesions. Based on this study, 99mTc-ECD SPECT is comparable to PWI in terms of its ability to detect acute stroke and is more useful than PWI in the case of subacute infarction.

Topics: Acute Disease; Adult; Aged; Brain Ischemia; Cysteine; Diffusion; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Perfusion; Radiopharmaceuticals; Stroke; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease.. Three equal-volume splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed.. In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5.. The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.

Topics: Acetazolamide; Adult; Aged; Aged, 80 and over; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebrovascular Circulation; Chronic Disease; Cysteine; Endarterectomy, Carotid; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon; Vasodilator Agents

Topics: Apraxias; Basal Ganglia; Brain; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Cysteine; Female; Glial Fibrillary Acidic Protein; Heart Transplantation; Humans; Liver Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Postoperative Complications; Radiopharmaceuticals; Speech; Thalamus; Tomography, Emission-Computed, Single-Photon

In acute ischemic stroke, the infarcted core is surrounded by a zone of tissue that has decreased perfusion. Some of this tissue may be salvaged by prompt, effective treatment. Diffusion-weighted MRI is sensitive in detecting the infarcted tissue, whereas SPECT also detects the hypoperfused tissue around the infarcted core. We studied the potential of combined diffusion-weighted MRI and SPECT to predict infarct growth and clinical outcome in patients not receiving thrombolytic treatment.. Sixteen patients with acute stroke were examined consecutively with diffusion-weighted MRI and 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPECT within 24 h of the onset of symptoms. Follow-up diffusion-weighted MRI was performed on the second day and after 1 wk. The volumes of infarcted and hypoperfused brain tissue were measured from diffusion-weighted MRI and SPECT, respectively. The volume difference between the hypoperfused and infarcted tissue on the first day was compared with the possible increase in infarct volume during the follow-up. Each patient's neurologic status was assessed with the National Institutes of Health Stroke Scale (NIHSS).. The volume of infarcted tissue increased from 48 +/- 54 cm3 (mean +/- SD) on the first day to 88 +/- 93 cm3 on the second day (P = 0.001) and to 110 +/- 121 cm3 at 1 wk (P = 0.001). The volume of hypoperfused tissue on the first day was significantly greater than the infarct volume (102 +/- 135 cm3; P = 0.001). The volume difference between the hypoperfused and infarcted tissue on the first day correlated significantly with the infarct growth between the first day and 1 wk (r = 0.71; P < 0.01). Between the first day and 1 wk, the increase of the infarct volume correlated significantly with the change in the NIHSS (r = 0.54; P < 0.05).. A large hypoperfusion zone around the infarct core in the acute phase of ischemic stroke predicts the infarct growth during the first week, and this correlates significantly with the change in the neurologic status of the patient. Combined diffusion-weighted MRI and SPECT performed within 24 h after the onset of symptoms can be useful in the evaluation of acute stroke to predict infarct growth.

Topics: Acute Disease; Aged; Aged, 80 and over; Brain; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Cysteine; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Although carotid shunting is occasionally necessary to prevent cerebral ischemia during carotid endarterectomy, there is no reliable indication for this procedure. The purpose of this study was to evaluate whether acetazolamide stress brain-perfusion SPECT can predict the need for carotid shunting during carotid endarterectomy.. Basal and acetazolamide stress brain-perfusion SPECT imaging was performed using a 1-d protocol and 99mTc-ethylcysteinate dimer (ECD) in 75 patients (12 women, 63 men; mean age, 64.8 y) before carotid endarterectomy. The need for carotid shunting during carotid endarterectomy was determined by the development of neurologic deterioration after carotid clamping under regional anesthesia. Regional cerebral blood flow, cerebrovascular reserve, the presence of contralateral carotid stenosis (> or =70%), and clinical risk factors, including age, sex, history of minor stroke or transient ischemic attack, diabetes mellitus, hypertension, and smoking, were assessed with regard to whether they could predict the need for shunting.. Carotid endarterectomy was performed safely without carotid shunting in 61 of 75 patients (81.3%). Carotid shunting was required in 14 patients (18.7%). Seven of 21 patients with a contralateral carotid stenosis, 9 of 41 with a reduced regional cerebral blood flow, and 11 of 30 with a reduced regional cerebrovascular reserve underwent carotid shunting. Patients with a reduced cerebrovascular reserve had a significantly higher number of carotid shunts performed (P < 0.01) than did those with a normal reserve, whereas contralateral carotid stenosis (P = 0.054) showed borderline significance. Reduced cerebral blood flow and clinical risk factors did not predict the need for carotid shunting (P > 0.1). Multiple logistic regression analysis showed that reduced cerebrovascular reserve was the only reliable predictor of the need for carotid shunting (P < 0.01). When a severely reduced cerebrovascular reserve (8/8) or reduced cerebral blood flow and cerebrovascular reserve with contralateral carotid stenosis (6/7) were present, carotid shunting was necessary, with positive and negative predictive values of 91% (10/11) and 94% (60/64), respectively.. A reduced cerebrovascular reserve can predict the development of cerebral ischemia during carotid clamping. Acetazolamide stress brain-perfusion SPECT may be useful as a complementary method in determining selective carotid shunting during carotid endarterectomy.

Topics: Acetazolamide; Adult; Aged; Aged, 80 and over; Brain; Brain Ischemia; Carotid Stenosis; Cerebrovascular Circulation; Cysteine; Endarterectomy, Carotid; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Predictive Value of Tests; 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

Topics: Adult; Brain; Brain Ischemia; Cysteine; Dominance, Cerebral; Female; Humans; Migraine Disorders; Organotechnetium Compounds; Regional Blood Flow; Tomography, Emission-Computed, Single-Photon

Because hippocampal neurons are quite vulnerable to the anoxic brain injury that sometimes occurs in aortic arch surgery in humans, hippocampal ischemia should be a sensitive indicator of global cerebral ischemia. It was concluded that the hypothermic retrograde cerebral circulation technique for aortic arch surgery could not only be performed safely with respect to the brain, but could also increase blood flow to the hippocampal areas, probably as a result of restoration of blood flow in the thoracic aorta.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm, Thoracic; Brain; Brain Ischemia; Cerebrovascular Circulation; Cysteine; Female; Hippocampus; Humans; Male; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

The aim of this study was to define the accuracy of 99mTc-ethyl cysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT) in distinguishing transient ischemic attack from completed ischemic stroke at early stages after the onset of symptoms. In a prospective study we examined 82 patients within 6 hours after the onset of symptoms (neurologic deficit caused by middle cerebral artery ischemia) using both 99mTc-ECD-SPECT and computed tomography (CT). The follow-up was based on Scandinavian Stroke Scale (SSS) 24 hours and 5-7 days, as well as on CT 7 days, after the event. SPECT evaluation was performed both visually and using semiquantitative region-of-interest (ROI) analysis. According to visual SPECT analysis, on admission 59 of 82 patients had activity deficits in the symptomatic hemisphere. After 7 days, all these patients had neurologic symptoms (SSS 28 +/- 12 points), caused by a cerebral infarction as evidenced with CT. Twenty-three of 82 patients displayed no early activity deficit despite clinical symptoms. None of these patients had neurologic symptoms after 7 days (indicating transient ischemic attack or prolonged reversible ischemic neurologic deficit). In the semiquantitative SPECT analysis, all patients had abnormal count densities in the respective ROI (activity < 90% compared with the contralateral side). All patients with transient ischemia (n = 23) had count rate densities more than 70% of the respective contralateral ROI, whereas all patients with subsequent infarction (n = 59) had values < 70%. Use of 99mTc-ECD-SPECT allows transient ischemia to be distinguished from ischemic infarction using relative regional activity thresholds within the first 6 hours after onset of symptoms.

Topics: Adult; Aged; Brain; Brain Ischemia; Cerebral Arteries; Cysteine; Diagnosis, Differential; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Time Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

To determine the value of perfusion computed tomography (CT) in a clinical study of patients with stroke and compare the results with single photon emission CT (SPECT) findings.. Perfusion CT was performed within 6 hours of symptom onset in 32 patients with possible stroke. Cerebral blood volume (CBV), cerebral blood flow (CBF), and time to peak contrast material enhancement were calculated on the basis of the CT results. Cerebral SPECT was also performed in a subgroup of 18 patients. Perfusion CT and SPECT findings were compared in a lesion-by-lesion analysis. Perfusion CT results were compared with follow-up CT and magnetic resonance imaging findings.. Areas of reduced CBF were detected with the aid of perfusion CT in 25 of 28 patients with a proved infarct (sensitivity, 89%). The results of the CBF maps corresponded well to SPECT findings in 13 (81%) of 16 patients, but ischemia was located outside the scanning level in the other three patients and was therefore missed. Perfusion CT revealed various changes in CBF, CBV, and time to peak enhancement in ischemic territories.. Perfusion CT not only allows early detection of cerebral ischemia but also yields valuable information about the extent of perfusion disturbances.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Ischemia; Cerebrovascular Circulation; Contrast Media; Cysteine; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Time Factors; Tomography Scanners, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

We evaluated 99Tcm-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl ester (99Tcm-ECD) dynamic and static SPET (single photon emission tomographic) images to examine 99Tcm-ECD kinetics under ischaemic cerebrovascular conditions. In 20 patients who showed arterial occlusion on magnetic resonance angiography, dynamic (0-10 min) and static (15-35 min) SPET images were acquired after the intravenous administration of 99Tcm-ECD. Thirteen of the patients had focal perfusion deficits that were more evident on the dynamic than on the static images; the other seven showed no such discrepancy. In those patients with a mismatch between the dynamic and static images, the extent corresponded to reduced vaso-reactivity to acetazolamide. Based on quantitative analysis of the ratio of tracer uptake in affected to that in unaffected areas, the patients with discrepant findings showed significantly different ratios on the dynamic and static images, whereas those with no such mismatch did not. Our results suggest that dynamic 99Tcm-ECD images provide circulatory information and that static images reflect a filling-in phenomenon of ECD metabolites in ischaemic lesions. 99Tcm-ECD dynamic and static SPET images offer an alternative method of detecting mild perfusion deficits without the need for acetazolamide challenge.

Topics: Acetazolamide; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Brain; Brain Ischemia; Carotid Stenosis; Cerebrovascular Circulation; Cysteine; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Topics: Aged; AIDS-Related Opportunistic Infections; Brain Ischemia; Brain Neoplasms; Cerebellar Neoplasms; Cerebral Infarction; Cysteine; Diagnosis, Differential; Fatal Outcome; Humans; Lymphoma, AIDS-Related; Male; Necrosis; Organotechnetium Compounds; Radiopharmaceuticals; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

Focal hyperaemia is a fairly common phenomenon in the subacute phase of an ischaemic stroke. This has rarely been reported with iodine-123 iodoamphetamine (IMP) and has never been identified using technetium-99m bicisate (99mTc-ECD). In this report, we present the case of a patient suffering from a left cerebral posterior stroke. 123I-IMP single-photon emission tomography (SPET) images showed a large area of significantly increased IMP activity located in the left occipital region whereas 99mTc-bicisate SPET displayed hypoactivity in the same area.

Topics: Amphetamines; Brain Ischemia; Cysteine; Humans; Hyperemia; Iodine Radioisotopes; Male; Middle Aged; Organotechnetium Compounds; Tomography, Emission-Computed, Single-Photon

The need for an agent to quantitatively measure regional cerebral blood flow in humans using single photon emission computed tomography has led to the development of a new 99mTc-labeled agent: bicisate (ethyl cysteinate dimer). We have utilized an acute stroke model in the baboon to examine the ability of this agent to quantitatively measure regional cerebral blood flow in ischemic tissue. One hour after occlusion of either the left anterior cerebral or the middle cerebral artery, 99mTc-bicisate was administered intravenously, followed 20 min later by the measurement of local cerebral blood flow using iodo-[14C]antipyrine. With use of double-label autoradiography, the distribution of 99mTc-bicisate was correlated with the local cerebral blood flow images. A cerebral blood flow parameter was calculated from the 99mTc-bicisate tissue distribution and the arterial blood tracer concentration using an indicator fractionation model. For cerebral blood flows above approximately 40-50 ml 100 g-1 min-1, 99mTc-bicisate underestimates cerebral blood flow by as much as 20%, while for blood flows below approximately 15 ml 100 g-1 min-1, blood flow is overestimated by the 99mTc-bicisate distribution by an average of 3-4 ml 100 g-1 min-1. This apparent hyperfixation at very low blood flows may be related to a higher extraction of this tracer by ischemic tissue.

Topics: Animals; Antipyrine; Brain; Brain Ischemia; Carbon Radioisotopes; Cerebrovascular Circulation; Cysteine; Male; Organotechnetium Compounds; Papio; Regression Analysis; Tomography, Emission-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