Kinichi Hisada

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of99mTc-ECD. Hemispherical brain perfusion indices (BPI) for99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between99mTc-ECD BPI and99mTc-HMPAO BPI and between99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,99mTc-ECD BPI was converted to133Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of99mTc-ECD were converted to rCBF maps using Lassens correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for99mTc-ECD SPET with those for99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor α of 2.6 gave nearly the same rCBF values for99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in99mTc-HMPAO studies is applicable to a99mTc-ECD study for the measurement of rCBF without any blood sampling.

A Study to Compare Oral Sumatriptan with Oral Aspirin plus Oral Metoclopramide in the Acute Treatment of Migraine

In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals

The accumulation of 201Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissues), and was not seen in necrotic tumor tissue regardless of the time after administration of 201Tl(I)-chloride. In inflammatory lesions, 201Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were croeded. Most 201Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of 201Tl(III)-chloride in tumor bearing animals was essentially the same as that of 201Tl(I)-chloride.

Distant metastases in differentiated thyroid carcinomas: A clinical and pathologic study

Of 514 patients with differentiated thyroid carcinoma treated between 1970 and 1987, 34 (6.6%) had distant metastases. Twelve patients died of their distant metastases; eight of these patients died within 5 years from the time of initial diagnosis. Death from cancer was most frequent in the seventh decade. The metastases were most often found in the lungs and bones. In the fatal group, pleural, brain, and pericardial metastases were noted. Local recurrences were found only in 24% of these 34 patients. Histologic types of primary thyroid tumors and metastatic tumors were reexamined and classified using our criteria, which were mainly based on the World Health Organization nomenclature and currently obtained pathologic observations of thyroid tumors. In 31 thyroid tumors, the surgical specimens were available for review. Twenty-four tumors were papillary and seven were follicular. Of the 24 papillary carcinomas, nine were follicular, eight were well-differentiated, and seven were trabecular. On the other hand, the seven follicular carcinomas consisted of four well-differentiated, two solid, and one oxyphilic. The majority of the thyroid tumors showed an extrathyroidal extension; however, two were intrathyroidal carcinomas and two were encapsulated carcinomas, larger than 5 cm in diameter. Distant metastases were confirmed morphologically in 18 patients (11 by surgical or biopsy material, five by autopsy, and two by cytology). The histologic types of metastatic tumors were consistent with those of primary thyroid tumors. Diagnostic 131I uptake was examined in 32 patients and absorption of diagnostic 131I in metastatic tumors was demonstrated in 21 patients. The 10-year survival rate of patients with 131I accumulating metastases (70%) was significantly better than that of patients with metastases lacking such uptake (40%). Immunoreactivity for thyroglobulin in metastatic tumors was correlated with the 131I absorption. This finding indicated that immunostaining of thyroglobulin in metastatic tumors might be useful in the prediction of the effectiveness of 131I therapy.

Quantitative analysis of 123I-metaiodobenzylguanidine (MIBG) uptake in hypertrophic cardiomyopathy

Myocardial scintigraphy with 123I-meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) was performed in 29 patients with hypertrophic cardiomyopathy (HCM) using whole-body scintigraphy and single-photon emission computed tomography (SPECT). Nonhypertensive patients were classified into three groups according to the septal thickness determined by ultrasonography; group 1 (wall thickness less than 16 mm, n = 5), group 2 (from 16 to 20 mm, n = 12) and group 3 (greater than 20 mm, n = 4). The regional myocardial uptakes of both 201Tl and 123I-MIBG (percent of injected dose/cm3 myocardium) were higher in the more hypertrophic septa. However, when regional MIBG uptake at 3 hours was divided by the 201Tl uptake to calculate the MIBG uptake per unit of blood flow, the hypertrophic septa showed lower mean values--0.39 +/- 0.23 and 0.50 +/- 0.10 in groups 3 and 2, respectively (p less than 0.1 compared with 0.69 +/- 0.20 in group 1). The regional MIBG clearance rate in the septum was significantly higher in group 3 compared with group 1 (13.4 +/- 8.0%/hr versus 1.5 +/- 6.2%/hr, p less than 0.05). The uptake and 123I-MIBG clearance rate in the lateral wall showed a similar tendency. Myocardial uptake determined by whole-body scintigraphy was slightly increased in group 2 (3.5 +/- 0.6%, p less than 0.05) compared with group 1 (2.7 +/- 0.8%); however, it was lower in group 3 (2.7 +/- 0.4%). Myocardial 123I-MIBG distribution demonstrated various patterns in comparison with 201Tl distribution, suggesting that flow-independent changes in sympathetic innervation or activity may exist in patients with HCM.(ABSTRACT TRUNCATED AT 250 WORDS)

SPECT analysis of regional cerebral blood flow changes in patients with schizophrenia during the Wisconsin card sorting test

Single photon emission computed tomography (SPECT) images were obtained in 10 right-handed neuroleptic-treated schizophrenic patients and 10 healthy volunteers using Tc-99m-hexamethyl-propylenamine oxime (Tc99m-HMPAO) during performance of the Wisconsin Card Sorting Test (WCST) and at rest. None of the patients showed severe impairment on the WCST. The patient group showed a statistically insignificant trend to incur more unique errors. In both the patient and control groups, the left lateral prefrontal blood flow significantly increased during the WCST, as compared to during resting conditions. Only during the WCST, the patient group showed a significant regional cerebral blood flow (rCBF) decline in the left medial prefrontal cortex, as well as in the right side under both the test and resting conditions. This left medial prefrontal rCBF during the WCST correlated positively with the number of unique errors, although this correlation was statistically insignificant. The right fronto-parietal rCBF was significantly increased in the patient group under both the test and resting conditions. Moreover, in the left hippocampal region, the patient group showed a significant rCBF increase under resting conditions.

Clinical Evaluation of Tumor Imaging with 201TI Chloride1

201TI was used as an imaging agent in 173 malignant tumors and 76 benign lesions. The sensitivity, specificity, and accuracy were 0.64, 0.61, and 0.63, respectively. Sensitivity was good in thyroid cancer (0.91) and fair in primary lung cancer (0.70) and primary liver cancer (0.71). Compared with 67Ga, 201TI appears to have a higher sensitivity in thyroid cancer and nearly the same sensitivity in primary lung cancer. 201TI might be useful in distinguishing cold thyroid nodules and in differentiating primary liver cancer from metastases.

Decreased 123I-MIBG uptake and increased clearance in various cardiac diseases.

123I-metaiodobenzylguanidine (MIBG), a tracer for sympathetic neuron integrity and function, was applied to 155 patients with various types of cardiac disease. The methods for quantification of MIBG and washout were studied as well as normal ranges. Heart-to-mediastinum average count ratio (H/M) correlated well with total heart count divided by injected activity (r=0.60, P< 0.0001 and r=0.72, P < 0.0001 for early and delayed images, respectively). Although as a whole left ventricular ejection fraction (LVEF) positively correlated with H/M ratio, decreased H/M ratio could be associated with normal LVEF, which may indicate that the MIBG activity was an independent variable compared with cardiac contractility. High washout rate was seen in various cardiac diseases, such as dilated cardiomyopathy, hypertrophie cardiomyopathy, ischaemic heart disease, hypertension, hypothyroidism and arrhythmia. The increased washout seems to be nonspecific to disease type, but is a common feature of damaged or failing myocardium.