Semi-quantitative assessment of cerebral blood flow with 99mTc-HMPAO SPET in type I diabetic patients with no clinical history of cerebrovascular disease

In 65 type I diabetic patients we prospectively evaluated brain perfusion by means of single-photon emission tomography after the injection of 740– 1110 MBq of technetium-99m hexamethylpropylene amine oxime. Thirty-five of the patients presented complications secondary to their diabetes. None showed CNS symptoms. A semiquantitative analysis was performed drawing 50 symmetrical regions of interest (ROIs) per patient. The relative contribution of each ROI to the total blood flow in each slice was compared with the relative contribution of the same ROI in a control group of ten healthy volunteers. Relative values of any ROI in the study group higher or lower than the mean ±2 SD in respect of the same ROI in the control group were considered abnormal. The results revealed hypoperfusion in 207 ROIs in the 65 patients with diabetes mellitus: of these ROIs, 113 were frontal, 10 frontotemporal, 20 temporal, 18 parietal, 11 occipital and 35 cerebellar. A total of 137 ROIs showed hyperperfusion: 17 frontal, 3 frontotemporal, 19 temporal, 18 parietal, 19 parieto-occipital, 29 occipital and 32 cerebellar. Out of 65 type I diabetic patients, 61 showed at least one hypoperfused ROI (P = 0.0064 vs. controls) and 25 showed more than three hypoperfused ROIs. None of the control subjects showed more than three hypoperfused regions (P<0.001). The results obtained demonstrate the existence of subclinical abnormalities of brain blood perfusion in patients with type I diabetes mellitus and no history of cerebrovascular disease, thereby allowing the initiation of intensive preventive measures. Received 16 July and in revised form 16 August 1997     

Cerebellar vasoreactivity in stroke patients with crossed cerebellar diaschisis assessed by acetazolamide and 99mTc-HMPAO SPECT.

Crossed cerebellar diaschisis (CCD) tends to persist or even worsen after supratentorial infarction. Several studies have shown impairment of cerebral vasomotor responsiveness in the hemispheric area of diaschisis in patients with hemispheric infarction. This finding has led to the concern that the lack of CCD reversibility might be associated with chronic circulatory abnormalities. We therefore assessed the vasoreactivity in the cerebellar hemisphere in which diaschisis is manifested using acetazolamide (ACZ) and SPECT. METHODS: Eight stroke patients with CCD (5 with unilateral hemispheric infarcts and 3 with unilateral intracerebral hemorrhage) had 99mTc-HMPAO SPECT scanning at rest and 20 min after intravenous injection of 1.0 g ACZ. The time interval after stroke ranged from 25 to 904 d. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as (unaffected - affected cerebellar hemisphere)/unaffected cerebellar hemisphere x100. RESULTS: After ACZ, the mean AI (8.7+/-6.6) was significantly decreased (P<0.05) compared with that at rest (17.7+/-5.8). Seven of the 8 patients showed decrease in the AI after ACZ. In 1 patient, the direction of the asymmetry was reversed after ACZ so that the AI was negative. The ACZ-induced change in the AI did not show a significant correlation with the time interval after stroke, whether calculated in absolute terms or as a percentage change. CONCLUSION: This study shows that normal vascular supply is maintained in the CCD-affected cerebellar hemisphere over long periods of time after a stroke. Thus, the lack of CCD reversibility may not be attributed to a chronic circulatory insufficiency. The results lend support to the concept of functional deactivation and subsequent transneuronal degeneration as a likely explanation for CCD. It is unclear whether decreased AI after ACZ indicates a higher vascular response of the affected cerebellar hemisphere than that of the normal side.     

Effects of treatment with OKT3 on brain perfusion in a heart transplant patient with SPET with 99mTc-HMPAO

A heart transplant patient treated with OKT3 developed a severe headache which worsened and was accompanied by a sudden decrease in the patient's consciousness level and aphasia when the treatment course was completed. CT was performed and was normal. SPET imaging with 99mTc-HMPAO of cerebral blood flow done 16 hours later revealed multiple and clear focal defects in the blood flow. Analysis of cerebral spinal fluid revealed aseptic pleocytosis. Five days after the completion of treatment, the symptoms remitted and a new control SPET 3 weeks later was completely normal. A diagnosis of neurotoxicity secondary to OKT3 administration was established.     

Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children

Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semiquantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se.     

Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children

Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semi-quantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se.     

Measurement of cerebral perfusion volume and 99mTc-HMPAO uptake using SPECT in controls and patients with Alzheimer's disease

Methods for quantifying the changes in brain function observed in single photon emission computed tomography (SPECT) using hexamethylenepropylene amine oxime (HMPAO) for patients with Alzheimer's disease have the potential of improving the diagnostic accuracy of the procedure and its ability to monitor response to treatment. The absolute percentage uptake of HMPAO and the cerebral perfusion volume (CPV) of the brain were assessed using SPECT in 26 patients with mild to moderate Alzheimer's disease (AD) and 24 control subjects. A subset of 15 control subjects, which was age-matched to the AD patients, was selected to allow fair statistical comparison of parameters between groups. The percentage of brain volume with reduced perfusion (R) and a volume loss index (VLI), given by /CPV, were also calculated. Eight of the control subjects were studied on a second occasion after a mean period of 6 months. There was no significant difference in percentage uptake between controls and AD patients, the mean value being 5.8%. Cerebral perfusion volume in controls was found to depend on sex (mean value in males and females being 1327 ml and 1222 ml, respectively) and on age. The volume loss index corrected for age and sex provided good discrimination between controls and AD subjects giving a sensitivity and specificity of 81% and 96%, respectively. The repeatability coefficient, the 95% confidence limit for the difference between repeat measurements, on controls was 67 ml (5%). The measurement of cerebral perfusion volume and related indices may be of value in identifying patients with early Alzheimer's disease and in following their response to treatment.     

Improved detection of cerebral hypoperfusion with internal carotid balloon test occlusion and 99mTc-HMPAO cerebral perfusion SPECT imaging.

A new method that employs a cerebral perfusion imaging agent, 99mTc-HMPAO, is described for identifying those patients who clinically pass an internal carotid artery balloon test occlusion but who then may develop a cerebral infarction after permanent occlusion. Test balloon occlusion of the internal carotid artery was performed in 17 patients, and 99mTc-HMPAO was injected intravenously while the balloon was inflated. The balloon was deflated and removed approximately 15-20 min later, and single-photon emission CT (SPECT) imaging of the brain was performed. In patients with an area of focal hypoperfusion, the 99mTc-HMPAO study was repeated the next day to determine if the hypoperfusion was due to the temporary balloon occlusion or to a preexisting abnormality. All 17 patients had normal neurologic examinations at the time of the balloon test occlusion. Fifteen had symmetric perfusion on the 99mTc-HMPAO SPECT scans. Five of these had permanent internal carotid artery occlusion, and four did not develop a neurologic deficit. One patient developed an ipsilateral watershed infarction after internal carotid artery occlusion during significant intraoperative hypotension. Two patients had ipsilateral regions of hypoperfusion with the test occlusion. Both these patients had repeat nonocclusion 99mTc-HMPAO SPECT studies that were normal. One patient is being followed. The second patient had ipsilateral EEG changes associated with temporary intraoperative occlusion of the internal carotid artery during aneurysm surgery. Although the numbers are relatively small, this study suggests that this protocol may be able to predict a good outcome after permanent carotid artery occlusion as well as to identify patients who are at greater risk for developing cerebral infarction after permanent occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative assessment of cerebral blood flow in subarachnoid haemorrhage by means of99mTc-HMPAO tomography

Regional hypoperfusion is a very frequent complication of subarachnoid haemorrhage (SAH), being related to vasospasm in the majority of cases. Twenty-six patients who were admitted for SAH underwent follow-up with technetium-99m hexamethylpropylene amine oxime single photon emission tomography (SPECT) 3 and 8 days after surgery. Fifteen patients of these had one more examination 15 days after surgery. The degree of hypoperfusion was quantified using an index of asymmetry which allow the comparison of two symmetrical regions of interest (ROIs) on the transaxial slice which presented the greatest perfusion defect. Comparison of CT data, transcranial Doppler data and clinical signs with the perfusion as quantified by^99mTc-HMPAO SPECT indicates that a difference in counts of less than 10% between the two symmetrical ROIs is of no diagnostic value. Follow-up of the brain perfusion clearly shows that the most pronounced hypoperfusion was observed just after surgery, with progressive normalization at 8 and 15 days after surgery.^99mTc-HMPAO SPECT performed 8 days after surgery allows prediction of the clinical outcome. For these reasons,^99mTc-HMPAO SPECT, which is the only method for follow-up of cerebral perfusion in routine clinical practice, should be the first examination to be performed after surgery in patients with SAH.     

99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression.

Compromised regional cerebral blood flow (rCBF) in major depressive disorder may be partly reversed by successful antidepressant treatment. However, it is not known if the reversal of rCBF compromise is dependent on the mode of antidepressant treatment. The current study aimed to address this question. METHODS: Thirty-three patients (19 women and 14 men; mean age +/- SD, 53 +/- 16 y) with moderate major depressive disorder were studied before 6 wk of treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, or a course of electroconvulsive therapy, and 31 of these patients were also studied afterward. A comparison group of 25 healthy volunteers (13 women and 12 men; mean age, 49 +/- 15 y) were studied once. rCBF was assessed using 99mTc-hexamethylpropyleneamine oxime SPECT. Images were analyzed using globally normalized statistical parametric mapping localized to the Montreal Neurologic Institute brain atlas. RESULTS: Baseline rCBF was lower in depressed patients than in controls in the frontal cortex and subcortical nuclei bilaterally. A response to medication was associated with normalization of rCBF deficits, whereas a response to electroconvulsive therapy was associated with an additional rCBF decrease in the parietotemporal and cerebellar regions bilaterally. CONCLUSION: Hypoperfusion in major depressive disorder largely normalizes after a response to pharmacotherapy. Perfusion changes after a response to electroconvulsive therapy may follow a different course.     

SPECT evaluation of brain perfusion reserve by the acetazolamide test using Tc-99m HMPAO

This report describes a new approach to the evaluation of brain perfusion reserve using Tc-99m HMPAO SPECT. Consecutive brain Tc-99m HMPAO SPECT studies before and after acetazolamide (Diamox) administration were performed within 30 minutes on 19 patients with significant vascular occlusive lesions. Thirteen patients showed decreased perfusion reserve and four patients maintained perfusion reserve in the affected vascular territories after Diamox administration, providing additional information to baseline Tc-99m HMPAO SPECT in 17 (89%) patients. Although flow augmentation post-Diamox was underestimated, possibly due to the nonproportionality of Tc-99m HMPAO activity to true blood flow, significant changes in the brain perfusion pattern were both visually and quantitatively determined using an image subtraction technique. This consecutive Tc-99m HMPAO SPECT technique seems to be of practical use for the evaluation of brain perfusion reserve and for the improvement of the sensitivity of detecting pathologic areas.     

Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (^99m-Te-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers — 40 young (mean age 29.5±6.3 years) and 28 aged (mean age 71.2±4.3 years) — were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (–1.01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.     

Simplified quantitative determination of cerebral perfusion reserve with H2 15O PET and acetazolamide

The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H₂¹⁵O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H₂¹⁵O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PR_nAA) and rCBF (PR_rCBF) (PR_nAA=0.843 PR_rCBF + 0.092, r=0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PR_nAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling.     

Principal component and volume of interest analyses in depressed patients imaged by 99mTc-HMPAO SPET: a methodological comparison

Previous regional cerebral blood flow (rCBF) studies on patients with unipolar major depressive disorder (MDD) have analysed clusters of voxels or single regions and yielded conflicting results, showing either higher or lower rCBF in MDD as compared to normal controls (CTR). The aim of this study was to assess rCBF distribution changes in 68 MDD patients, investigating the data set with both volume of interest (VOI) analysis and principal component analysis (PCA). The rCBF distribution in 68 MDD and 66 CTR, at rest, was compared. Technetium-99m d,l-hexamethylpropylene amine oxime single-photon emission tomography was performed and the uptake in 27 VOIs, bilaterally, was assessed using a standardising brain atlas. Data were then grouped into factors by means of PCA performed on rCBF of all 134 subjects and based on all 54 VOIs. VOI analysis showed a significant group × VOI × hemisphere interaction (P<0.001). rCBF in eight VOIs (in the prefrontal, temporal, occipital and central structures) differed significantly between groups at the P<0.05 level. PCA identified 11 anatomo-functional regions that interacted with groups (P<0.001). As compared to CTR, MDD rCBF was relatively higher in right associative temporo-parietal-occipital cortex (P<0.01) and bilaterally in prefrontal (P<0.005) and frontal cortex (P<0.025), anterior temporal cortex and central structures (P<0.05 and P<0.001 respectively). Higher rCBF in a selected group of MDD as compared to CTR at rest was found using PCA in five clusters of regions sharing close anatomical and functional relationships. At the single VOI level, all eight regions showing group differences were included in such clusters. PCA is a data-driven method for recasting VOIs to be used for group evaluation and comparison. The appearance of significant differences absent at the VOI level emphasises the value of analysing the relationships among brain regions for the investigation of psychiatric disease.     

Differences in vasodilatory capacity and changes in cerebral blood flow induced by acetazolamide in patients with cerebrovascular disease.

To investigate changes in cerebral blood flow (CBF) and blood volume induced by acetazolamide (ACZ) in patients with a variable autoregulatory status responding to reduced perfusion pressure, PET measurements of hemodynamic parameters were performed on patients with cerebrovascular disease, and the relationships between the parameters were evaluated. METHODS: Sixteen patients with unilateral major cerebral arterial occlusive disease underwent PET studies with (15)O-gas and the steady-state method to obtain hemodynamic parameters in the brain. All patients and 8 healthy volunteers underwent H(2)(15)O PET at baseline and 10 min after ACZ injection to calculate the CBF and arterial-to-capillary blood volume (V(0)) based on a 2-compartment model. RESULTS: The regional CBF (rCBF) and V(0) increased significantly after ACZ administration in volunteers and in the hemisphere contralateral to the ischemic side in patients. However, in a subgroup of patients with disease who showed a significant reduction in the rCBF increase in the ipsilateral hemisphere, the ACZ challenge caused a decrease in the rCBF even though the V(0) showed a significant increase. The reduction in the rCBF increase was associated with an asymmetric increase in oxygen extraction fraction (OEF) but not with an absolute OEF increase. CONCLUSION: The increases in rCBF and V(0) induced by ACZ administration, as well as absolute OEF value in the baseline condition, did not necessarily parallel each other in the ipsilateral hemispheres of patients. Thus, the increase in rCBF after ACZ challenge may not represent vasodilatory capacity in patients with cerebrovascular disease, especially in the regions with a reduced rCBF response.     

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable. Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.