Tc-99m HMPAO to demonstrate diffuse cortical necrosis in vivo

Tc-99m hexamethylpropylene amineoxime (HMPAO) is a novel radiopharmaceutical demonstrated to be a sensitive indicator of abnormalities of cerebral perfusion. Most reports in the literature have evaluated patients with gross perfusion deficits, such as cerebrovascular accidents, and with dementia, where patterns of diffuse perfusion deficit were reported comparable with those seen in PET studies. We report a patient in whom there was the rapid onset of dementia, with the HMPAO images demonstrating diffuse loss of cortical perfusion in a nonfocal, and nonsegmental, fashion. Correlation with postmortem examination demonstrates good concordance between the diffuse nature of HMPAO loss, and diffuse cortical necrosis throughout both cerebral hemispheres. The technique was shown to be more sensitive than transmission CT scanning in demonstrating the extent of the deficit, and it correlated closely with the functional deficits noted in the patient.     

Comparison between cortical distribution of I-123 iomazenil and Tc-99m HMPAO in patients with Alzheimer's disease using SPECT.

PURPOSE: To compare brain perfusion and synaptic density in Alzheimer's disease assessed using I-123 iomazenil SPECT with brain perfusion assessed using Tc-99m HMPAO SPECT. MATERIALS AND METHODS: Early and delayed I-123 iomazenil SPECT images acquired 20 and 180 minutes after injection were compared with Tc-99m HMPAO SPECT studies acquired 15 to 20 minutes after injection in five patients with Alzheimer's disease. RESULTS: Visual analysis of I-123 iomazenil images showed more severe (n = 4) and extensive (n = 3) defects than did Tc-99m HMPAO. Semiquantitative analysis was performed by normalizing the uptake of Tc-99m HMPAO and I-123 iomazenil in individual brain regions in the cerebellum and expressing these values as a ratio of the occipital regions. The analysis of brain regional ratios in Tc-99m HMPAO studies showed a low but significant correlation with ratios of delayed (r = 0.325, P < 0.05) images in the I-123 iomazenil studies. Furthermore, when compared with Tc-99m HMPAO, early (P < 0.01) and delayed mean ratios (P < 0.05) were significantly less in the frontal regions; early mean ratios were significantly less in the temporal regions (P < 0.05), and delayed (P < 0.05) mean ratios were significantly less in the parietal regions. CONCLUSIONS: Tc-99m HMPAO images were better correlated with I-123 iomazenil images, indicating cortical synaptic density (delayed images). I-123 iomazenil SPECT in patients with Alzheimer's disease provided more sensitive information than Tc-99m HMPAO, allowing evaluation of brain perfusion and synaptic density.     

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.     

Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease.

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinson's disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinson's patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinson's disease is similar to that seen in Alzheimer's disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinson's disease may be similar to that in Alzheimer's disease.     

A bullseye display of regional perfusion of the brain

The authors submit a method of viewing Tc-99m HMPAO SPECT images of the brain based on the principles of the myocardial bullseye or polar mapping. Commercially available software for the production of a myocardial bullseye display is suitable for the preparation of a bullseye display of regional perfusion image of the brain. This display facilitates the detection of cerebral cortical perfusion defects by displaying all SPECT oblique slices concentrically from base to vertex in a single image.     

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.     

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (^99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n=19), presumed Pick's disease (n=5), idiopathic Parkinson's disease with dementia (DPD, n=15) and progressive supranuclear palsy (PSP, n=5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups. Offprint reprints to: M.O. Habert     

Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.     

Cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients. Comparison between EEG, X-ray CT, and Tc-99m HMPAO

Thirteen mentally retarded pediatric patients aged 4 to 13 years with therapy-resistant epilepsy underwent Tc-99m HMPAO brain perfusion SPECT studies. The results (abnormal in 12 of the 13 patients) were compared with EEG results in 12 of the 13 patients (abnormal in all 12) and x-ray CT in 11 of the 13 patients (normal in 9). Patients with spikes on EEG had foci of increased uptake on HMPAO. This study confirms that HMPAO is sensitive in detecting perfusion abnormalities and localizing epileptic foci in this group of patients.     

Regional cerebral perfusion and amytal distribution during the Wada test.

The distribution of sodium amytal and its effect on regional cerebral perfusion during the intracarotid amytal (Wada) test were investigated using high-resolution hexamethyl propyleneamine oxime (HMPAO) SPECT coregistered with the patient's MRI dataset. METHODS: Twenty patients underwent SPECT after intravenous HMPAO injection, and 5 patients had both intravenous and intracarotid injections in a double injection-acquisition protocol. RESULTS: All patients had hypoperfusion in the territories of the anterior and middle cerebral arteries. Basal ganglia perfusion was preserved in 20 of 25 patients. Hypoperfusion of the entire mesial temporal cortex was seen in 9 of 25 patients. Partial hypoperfusion of the whole mesial cortex or hypoperfusion of part of the mesial cortex was seen in 14 of 25 patients. In 2 of 25 patients, mesial temporal perfusion was unaffected. In 5 patients, the double acquisition showed a distribution of HMPAO delivery matching that of hypoperfusion, except for the following: (a) HMPAO was delivered to the basal ganglia and insula, where there was no hypoperfusion; (b) HMPAO was not delivered to the contralateral cerebellum, which did show hypoperfusion; and (c) in 1 patient, perfusion of the mesial temporal cortex was preserved despite intracarotid delivery of HMPAO. CONCLUSION: Some degree of hypoperfusion of medial temporal structures occurs in the great majority of patients during the Wada test. Partial inactivation of memory structures is therefore a credible mechanism of action of the test. The double acquisition protocol provided no evidence that mesial temporal structures are inactivated remotely by diaschisis. Perfusion in the basal ganglia and insular cortex is not affected by amytal.     

Magnetic resonance perfusion imaging in malformations of cortical development

BACKGROUND: Malformations of cortical development vary in neuronal maturity and level of functioning. PURPOSE: To characterize regional relative cerebral blood volume (rCBV) and difference in first moment transit time (TTfm) in polymicrogyria and cortical tubers using magnetic resonance (MR) perfusion imaging. MATERIAL AND METHODS: MR imaging and dynamic T2*-weighted MR perfusion imaging were performed in 13 patients with tuberous sclerosis complex, 10 with polymicrogyria, and 18 controls with developmental delay but no macroscopic brain abnormality. Regions of interest were placed in cortical tubers or polymicrogyric cortex and in the contralateral normal-appearing side in patients with malformations. In "control" subjects, regions of interest were placed in the frontal and parietal lobes in both hemispheres. The rCBV and TTfm of the tuber/contralateral side (rCBV(R)TSC and DeltaTT(FM)TSC) as well as those of the polymicrogyria/contralateral side (rCBV(R)PMG and DeltaTT(FM)PMG) were assessed. The right-to-left asymmetry of rCBV and TTfm in the control group was also assessed (rCBV(R)Controls and DeltaTT(FM)Controls). RESULTS: There was no significant asymmetry between right and left rCBV or TTfm (P>0.05) in controls. There was significant reduction in rCBV(R)TSC compared to rCBV(R)Controls (P<0.05), but no significant difference in DeltaTT(FM)TSC compared to DeltaTT(FM)Controls (P>0.05). There were no significant differences between rCBV(R)PMG and rCBV(R)Controls (P>0.05) or DeltaTT(FM)PMG and DeltaTT(FM)Controls (P>0.05). CONCLUSION: Our findings imply that cerebral blood volume of polymicrogyria is similar to normal cortex, but there is reduced cerebral blood volume in cortical tubers. The lower rCBV ratio of cortical tubers may be related to known differences in pathogenetic timing of the underlying abnormalities during brain development or the presence of gliosis.     

Watershed infarcts, Tc-99m HMPAO SPECT and CT correlation. Case reports

We report on the use of Tc-99m hexamethylpropylene amineoxime (HMPAO) in watershed infarcts in five patients who had focal neurologic symptoms. Good correlation between Tc-99m HMPAO and CT was found in two patients. In three patients only Tc-99m HMPAO SPECT in a watershed distribution showed a perfusion abnormality that explained the clinical findings. Tc-99m HMPAO SPECT may be more sensitive than CT in the detection of infarctions in the watershed distribution.     

Evaluation of brain perfusion SPECT imaging using 99mTc-ECD

Fundamental and clinical evaluation was performed on 99mTc-ECD, a new agent for brain perfusion SPECT. Radiochemical purity reaches a plateau of approximately 98% at 30 min after reconstitution and remains stable up to 24 hours later. A biodistribution study showed approximately 5% injected dose in the brain, very slow brain washout of 5.6% per hour on the average, and rapid washout from the other organ mainly through the urinary system. Brain ECD distribution was determined within 2 min postinjection and remained stable for up to 1 hour. Three hours later, slight but significant changes in brain distribution were observed, that were relative reduction of cerebral cortical activity and gray to white matter activity ratio, and relative elevation of white matter and thalamic activities. Comparative studies of ECD images with IMP and HMPAO images revealed that radioactivity contrast between affected and unaffected areas was less prominent in ECD than in IMP in cerebral and cerebellar cortical lesions, more prominent in ECD than in IMP in striatal and thalamic lesions, and somewhat more prominent in ECD than in HMPAO in both lesions. Imaging around 1 hour postinjection seems to be more appropriate than immediate postinjection imaging because of the clearance of the extracranial radioactivity and somewhat better radioactivity contrast between affected and unaffected areas.     

Technetium 99m HMPAO scanning in patients with subarachnoid haemorrhage: a preliminary study

Technetium 99m hexamethylpropylene amine oxime (HMPAO) is an agent which, when injected intravenously, gives images which reflect cerebral blood flow. Seven patients who had suffered subarachnoid haemorrhage were examined by cerebral angiography and by 99Tcm HMPAO scanning. The two studies were compared and in six cases there was evidence of decreased cerebral perfusion in relation to the ruptured aneurysm causing the subarachnoid haemorrhage. In one case no cause for the haemorrhage was demonstrated angiographically, and the HMPAO study was normal. In two of the six cases, spasm of the cerebral artery distal to the ruptured aneurysm was seen angiographically and it appears that 99Tcm HMPAO scanning does not correlate with gross arterial spasm but reflects smaller degrees of cerebral underperfusion not demonstrable by angiography. The results demonstrate a relationship between local decreased cerebral perfusion and ruptured cerebral aneurysm and may be of use in determining which aneurysm has bled in patients who have more than one aneurysm demonstrated angiographically.     

Increased brain retention of Tc-99m HMPAO following acetazolamide administration

Sixty-five patients referred for Tc-99m HMPAO SPECT brain perfusion studies had measurements of global Tc-99m HMPAO retention after injection at rest and after acetazolamide pretreatment. Acetazolamide produced relative changes in Tc-99m HMPAO retention similar to those previously reported with Xe-133 regional cerebral blood flow (rCBF) measurements. This addition to imaging protocols allows another objective evaluation of the cerebral vascular reserve.     

Correlation of magnetic resonance imaging findings with hexamethylpropyleneamine oxime brain single photon emission computed tomography in ischemic stroke patients in the subacute stage

PURPOSE: To evaluate the correlation between magnetic resonance imaging (MRI) findings and 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) during the subacute stage in ischemic stroke patients. MATERIAL AND METHODS: The T1 and T2-weighted images and brain SPECT findings of 84 patients (mean age 60.69 +/- 12.47 years) with subacute cerebral ischemia during the period 1998-2004 were reviewed. All HMPAO SPECT and MRI studies were performed between 3 and 7 days (mean time delay 4.76 +/- 1.29 days) after the onset of stroke symptoms. RESULTS: An ischemic lesion was seen both in T1 and T2-weighted images with perfusion defects above 60% (severe defect) according to count/pixel data of the lesion in HMPAO SPECT studies in 30 (90.9%) of 33 patients. Otherwise, the ischemic lesion was seen only on T2-weighted images with perfusion defects between 30% and 60% (moderate defect) in HMPAO SPECT studies in 25 (89.3%) of 28 patients. In 20 (87%) of 23 patients who had perfusion defects below 30% (mild defect) on HMPAO SPECT, only non-specific findings such as cerebral atrophy and/or periventricular ischemic-gliotic lesions could be seen in MRI. The difference between these ratios was statistically significant (P < 0.01). CONCLUSION: Brain 99mTc-HMPAO SPECT findings indicate good correlation with MRI findings. When the ischemic lesions could be seen in both T1 and T2-weighted images, the patients frequently had severe perfusion defects. When only seen in T2-weighted images, the perfusion defect was moderate. When only non-specific findings were revealed by MRI, only mild perfusion defects were found by SPECT.     

Tc-99m HMPAO SPECT of the brain in the neonate

A brain scan with Tc-99m hexamethylpropyleneamineoxime (HMPAO) performed on a neonate demonstrated normal localization only in the sensorimotor cortex, basal ganglia, and cerebellum. This pattern of localization is remarkably similar to previously published PET images of the neonate. Because Tc-99m HMPAO is readily available and has biochemical and physical characteristics that are suitable for perfusion imaging of the brain, it likely will become a major imaging agent in nuclear medicine. Normal scan findings in the neonatal age group with Tc-99m HMPAO have not been previously reported because of limited clinical use to date.     

Technetium-99m hexamethylpropylene amine oxime single photon emission tomography of the brain in early Parkinson's disease: correlation with dementia and lateralization

Regional cerebral blood flow was assessed in 19 patients with early idiopathic Parkinson's disease (PD) and 12 control subjects of similar age by single-photon emission tomography using technetium-99m hexamethylpropylene amine oxime (HMPAO). Of the patients with PD, seven were mildly demented and 15 presented with hemiparkinsonism. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. Mean cortical and regional uptake ratios in non-demented PD patients were not significantly different from values in the controls. In contrast, besides generalized cortical hypoperfusion, demented PD patients had significantly lower HMPAO uptake in the frontal and basal ganglia regions than non-demented patients. These observations support the hypothesis of impaired neuronal activity in both cortical and subcortical regions of the brain in demented PD patients. In hemiparkinsonian patients, the only asymmetrical finding was a relative hypoperfusion in the contralateral parietal region. This may be due to deafferentation of the thalamoparietal pathways. The lack of asymmetrical uptake in basal ganglia in our PD patients may be explained by their staging at the time of the investigation (stage I and II, Hoehn and Yahr scale).Correspondence to: Hsiu-Chih Liu     

Cerebral perfusion imaging with technetium-99m HMPAO following cerebral trauma. Initial experience

Thirteen patients with cerebral trauma were studied for cerebral perfusion by the use of Tc-99m HMPAO scanning. CT imaging was performed on nine patients. Because of their clinical condition, four patients were scanned only in the planar mode to help establish the diagnosis of brain death. Other indications for study included gunshot wound and blunt or sharp object trauma with or without skull fracture. In all cases, HMPAO scans showed defects with a quality equivalent to or greater than that demonstrated by CT. Our initial results suggest that HMPAO may predict the degree of permanent damage and which patients may develop post-traumatic headache. A diagnosis of brain death can be established without the withdrawal of medical therapy.     

Embolic distribution through patent foramen ovale demonstrated by (99m)Tc-MAA brain SPECT after Valsalva radionuclide venography.

Cryptogenic stroke might relate to paradoxical embolism stemming from right-to-left shunt caused by patent foramen ovale (PFO). We performed radionuclide venography using the Valsalva maneuver, followed by (99m)Tc-macroaggregated albumin (MAA) brain SPECT to investigate the fate of emboli originating from the lower extremities. METHODS: Ten patients (9 men, 1 woman; mean age, 61 +/- 17 y) with PFO underwent radionuclide venography with and without the Valsalva maneuver on the whole-body image, followed by brain SPECT with (99m)Tc-MAA to determine the cortical uptake that would detect right-to-left shunt. After counts in each region of interest (ROI) were normalized by comparison with the averaged count, the distribution of MAA was compared with that of (99m)Tc-hexamethyl-propyleneamine oxime (HMPAO) brain SPECT by drawing ROIs on frontal, temporoparietal (anterior circulation territory), occipital, and cerebellar areas (posterior circulation territory). RESULTS: The thyroid on the whole-body scan was visualized after the Valsalva maneuver in 2 of the 10 patients. In 7 of 10 patients, 56 ROIs in the visualized cortical uptake showed that the distribution of MAA correlated well with that of HMPAO according to the equation: HMPAO = -71.21 + 1.71 x MAA, (r = 0.575, P < 0.01). The excess difference in the relative counts in the posterior over anterior circulation territory was 5.6% and 16.1% of the HMPAO and MAA values, respectively. CONCLUSION: Brain SPECT with (99m)Tc-MAA was more sensitive than thyroid visualization in detecting right-to-left shunt. The excess flow in the posterior cerebral circulation indicated an increased likelihood of cerebral emboli originating from the lower extremities and indicated that the flow difference between HMPAO and MAA probably resulted from poor linearization of HMPAO in the high-flow area.