Hisashi Sumiya

A quantitative approach to technetium-99m hexamethylpropylene amine oxime.

A non-invasive, simple method for the quantitative evaluation of brain perfusion is presented using intravenous radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (ku of the tracer from the blood to the brain. The ku values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of ROIbrain size to ROIaorta size at 10. The wholebrain BPI values for the normal control subjects showed a significant negative correlation with advancing age (r = -0.632, P =0.0204, n =13). The mean of the wholebrain BPI of 7.0 (SD =1.4) in 20 patients with cerebrovascular disorders was significantly lower than that of 10.6 (SD =1.5) in 13 normal control subjects. The BPI measurements showed only minimal intra- and interobserver variability. Changes of the ratio of ROIaorta size and ROIbmin size did not significantly influence the BPI values. Hemispherical BPI values in 19 subjects (n =38) showed highly significant correlations with the hemispherical mean cerebral blood flow values obtained from Xenon-133 single photon emission tomography (SPET) (r =0.926, P =0.0001 for the early picture method and r =0.932, P =0.0001 for the sequential picture method). This technique is easy to apply as an adjunct to SPET and may be helpful in the quantitative evaluation of brain perfusion in routine clinical studies.

Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassens correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor α was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/ 100 g/min on average. An increase in rCBF after acetazolamide administration was observed and mesured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow.

High resolution Tc-99m HMPAO SPECT in a patient with transient global amnesia.

This is a report of a patient who underwent high-resolution brain perfusion SPECT studies during and after an episode of transient global amnesia. During the attack, SPECT imaging showed increased perfusion in the left medial temporal region involving the amygdala and hippocampus. After recovery from amnesia, a follow-up SPECT examination showed slightly decreased perfusion in this region. These findings support the hypothesis that transient global amnesia is associated with transient hyperperfusion in the medial temporal brain structures, and confirm the utility of high-resolution SPECT imaging for the evaluation of the fine details of functional brain anatomy.

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.

Determination of Flow and Rate Constants in a Kinetic Model of [99mTc]-Hexamethyl-Propylene Amine Oxime in the Human Brain

The values for flow and rate constants for a kinetic model of [99mTc]–hexamethylpropyleneamine oxime (HM-PAO) distribution in the human brain were determined. The single-pass extraction ratio of HM-PAO was also determined in the rat brain by the indicator diffusion method; a value of 0.90 ± 0.02 (mean ± SEM, n = 5) was obtained. Time course data of brain activity and arterial blood activity of the tracer were fitted to a four compartment model: Values of blood flow and the firstorder rate constants for backdiffusion of the diffusible tracer from brain to blood (k2), conversion of the lipophilic tracer to the hydrophilic one in brain (k3), and conversion of the diffusible tracer to the nondiffusible one in blood (k5) were determined. Conversion of hydrophilic tracer back to a lipophilic form in both blood and brain was assumed to be negligible during the course of the experiment. The values obtained for blood flow, k2, and k3 were, respectively, 0.40 ± 0.03 ml/g/min, 0.38 ± 0.04 min−1, and 0.92 ± 0.05 min−1 in the gray matter (n = 4), and 0.23 ± 0.01 ml/g/min, 0.17 ± 0.01 min−1, and 1.01 ± 0.05 min−1 in the white matter (n = 2) in patients with cerebrovascular disorder. The k5 value was 1.14 ± 0.06 min−1 (n = 4). These experimentally determined values agree well with the theoretical ones previously reported by Lassen et al. The results suggest the relative constancy of the k3 and k5 values and the more prominent initial backdiffusion of the lipophilic HM-PAO from brain to blood in high flow regions compared to low flow regions.

Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task

Regional cerebral blood flow (rCBF) was measured in 11 schizophrenic patients amid 10 normal controls, both at rest and while performing an auditory discrimination task. Single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was used for quantitative evaluation of rCBF. The schizophrenic patients showed greater rCBF in the temporal and parietal regions at rest than the controls, but no abnormalities were found in frontal perfusion. During task performance. on the other hand, the patients showed a reduced frontal rCBF. whereas there was no group difference in rCBF in the temporal and parietal regions. In addition, the left> right hemisphere asymmetries of rCBF observed in the controls during task performance were not present in the patients. although there was no group difference in hemisphere laterality in rCBF at rest. These findings suggest that the employment of a cognitive task for neuroimaging studies is useful for detecting abnormalities of brain activation. such as hypofrontality and altered hemisphere laterality. in patients with schizophrenia.

Acetazolamide effect on vascular response in areas with diaschisis as measured by Tc-99m HMPAO brain SPECT.

The effects of acetazolamide (Diamox®) on vascular response were investigated in areas with intrahemispheric thalamic diaschisis and crossed cerebellar diaschisis using consecutive Tc-99m HMPAO brain SPECT studies before and after Diamox administration. All six patients with thalamic diaschisis and five of eight patients with crossed cerebellar diaschisis at baseline showed significantly augmented perfusion after Diamox administration in the affected thalamus and cerebellum compared with that in the contralateral unaffected areas. These results suggest more dilatation of the arterioles in areas with diaschisis after Diamox administration than in areas without diaschisis. Diamox may produce relative luxury perfusion in areas with diaschisis.

Intense Ga-67 uptake in adenosquamous carcinoma of the pancreas

Gallium-67 citrate (Ga-67) scintigraphy was performed in a patient with adenosquamous carcinoma of the pancreas. Intense and homogeneous uptake was observed in the tumor. Few reports have dealt with Ga-67 findings in pancreatic cancers. Ga-67 uptake in the tumor was assumed to be due to accumulation in the component of squamous cell carcinoma. This case suggested that Ga-67 citrate scintigraphy may be useful in detecting adenosquamous carcinoma of the pancreas. To our knowledge, no report has described findings of Ga-67 citrate scintigraphy of adenosquamous carcinoma of the pancreas. Radiologists should remember adenosquamous carcinoma of the pancreas when encountering such scintigraphic findings.

Synthesis of radioiodinated analogs of 2-(4-Phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent

Three iodovesamicol analogs, iodinated at the ortho, meta, and para positions of the 4-phenylpiperidine moiety, were synthesized and labeled with 125I by isotopic exchange reaction. Their potencies as a vesamicol-like drug were evaluated with competitive inhibition studies using (-)[3H]vesamicol. The radiochemical yields were 40-85%, the radiochemical purities exceeded 95% and their specific activities were 370-740 GBq/mmol. The descending order of binding affinity of the tested compounds against the vesamicol receptor was m-iodovesamicol > o-iodovesamicol > p-iodovesamicol. The receptor binding affinity of m-iodovesamicol (IC50 = 133 nM) was comparable with that of vesamicol (IC50 = 109 nM). Therefore, the meta position of the 4-phenylpiperidinyl fragment of vesamicol was the optimum site for iodination, and radioiodinated m-iodovesamicol may serve as a useful radiopharmaceutical for in vitro and in vivo studies of presynaptic cholinergic neurons in rats.

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml.100 g−1.min−1 with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.