Sadahiko Nishizawa

A Multicenter Validation of Regional Cerebral Blood Flow Quantitation Using [123I]Iodoamphetamine and Single Photon Emission Computed Tomography

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54×) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects; y = 2.0 + 0.80×). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55×). Mean cortical gray matter rCBF in a group of normal subject was 43.9 ± 3.3 and 43.4 ± 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml ± 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = −3.21 + 1.07×, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

SPECT with 99mTc]-d,l-Hexamethyl-Propylene Amine Oxime (HM-PAO) Compared with Regional Cerebral Blood Flow Measured by PET: Effects of Linearization

In order to validate the use of technetium-99m–d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a “linearization algorithm” to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p < 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

A functional MRI analysis of comprehension processes of Japanese sentences

WE tried to identify the mechanisms directly related to syntactic processing in an fMRI experiment using strictly controlled sets of verbal stimuli. In two conditions, center-embedding and left-branching conditions, the same sets of words were used to construct stimulus sentences, while only the word order reflecting their syntactic structure was different. The subjects task was to understand the relationship among three characters mentioned in the sentences. A difference of activation in Brocas area (BA44 and 45) between the two conditions was found. This result suggests that these areas are involved in syntax-related processing. Furthermore, it was suggested that the posterior part of the frontal lobe (BA6/9) and the inferior parietal area (BA39/40) are involved in the understanding of the relationship among the three characters mentioned in each sentence.

Naming of animals and tools : a functional magnetic resonance imaging study of categorical differences in the human brain areas commonly used for naming visually presented objects

To investigate the neural substrates for naming objects and their category-dependency, we performed functional magnetic resonance imaging (fMRI) with naming of animals and tools. Naming objects, irrespective of their category, activated left frontal to bilateral parietal regions and occipital to posterior temporal regions. Within these areas, naming animals caused more activation of the primary visual cortex bilaterally and the ventral occipital cortex to the inferior temporal area on the right side. Naming tools caused more activation of the posterior part of the left middle temporal area, the rostral part of the left inferior parietal lobule, and the left inferior frontal cortex. These findings suggest that the neural network for naming objects has discrete category-dependent nodes through which pertinent conceptual knowledge may be mediated.

Neural substrates for depth perception of the Necker cube ; a functional magnetic resonance imaging study in human subjects

We have studied the cerebral activity for the depth perception of the Necker cube by functional magnetic resonance imaging. Three types of line drawing figures were used as stimuli, the Necker cube, hidden line elimination cube and overlapping squares. Subjects were instructed to perceive both orientations of the depth of the Necker cube. They were instructed to shift their attention voluntarily during viewing overlapping squares to obtain a control for the attentional shift in perceiving the Necker cube. A hidden line elimination cube was used as a control for monocular stereopsis. The results showed a clear symmetrical activation in premotor and parietal areas during the Necker cube perception compared with other conditions. The present result suggests that a neural process similar to mental image manipulation occurs during depth perception of the Necker cube.

Glucose consumption in recurrent gliomas.

In order to investigate the clinical significance of glucose consumption (GC) in recurrent gliomas, positron emission tomography with 18F-labeled fluorodeoxyglucose was measured in 18 cases of histologically verified recurrent gliomas. The GC of the tumors were categorized into four groups. Five tumors were in Group IV, the highest GC, four were in Group III, eight were in Group II, and one was in Group I. Masses in Groups III and IV were clearly defined as a hot spot higher than or similar to the GC of the contralateral cortex. Half of the recurrent gliomas showed the lower GC of Group I or II, but two thirds of these were histologically high-grade gliomas. Although GC in the recurrent gliomas did not always increase as expected, a focal increase of GC, even mild and small, in the area of previous surgery is diagnostically important. Tumors with high GC showed high histological malignancy, irrespective of tissue damage. Patients with tumors of low GC had longer survival rates than those with high GC, although statistical significance was not obtained. Thus, positron emission tomography with 18F-labeled fluorodeoxyglucose was useful for detecting the recurrence of gliomas and suggesting their histological malignancy and prognosis. Care should be taken because viable tumor cells could be present in areas of low GC and small recurrent masses could be missed because of the poor spatial resolution of positron emission tomography.

Prospective Evaluation of Whole-Body Cancer Screening With Multiple Modalities Including [18F]Fluorodeoxyglucose Positron Emission Tomography in a Healthy Population: A Preliminary Report

PURPOSE To prospectively evaluate the utility of whole-body cancer screening with multiple modalities including [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) in a healthy population. This report summarizes the results of the first three annual screenings. PARTICIPANTS AND METHODS A total of 1,197 healthy volunteers > or = 35 years old were enrolled between August 2003 and July 2004 and offered annual cancer screening for 5 years with subsequent long-term follow-up. Screening modalities included were whole-body FDG-PET, chest and abdominal computed tomography (CT), brain and pelvic magnetic resonance imaging, several tumor markers, and fecal occult blood testing. RESULTS As of the end of 2006, 22 primary cancers were pathologically confirmed. Nineteen of 22 were detected by the screening; 18 in the initial, one in the second, and none in the third. Three were diagnosed after development of symptoms. Of the 18 detected in the initial screening (six thyroid, four lung, three prostate, three breast, one endometrial, and one thymic), 12 were at stage I and 11 were PET positive. PET-negative cancers were detected by CT or the prostate-specific antigen (PSA) test. Sensitivity and specificity were 50.0% (11 of 22) and 93.2% (1,095 of 1,175), respectively, for FDG-PET alone and 81.8% (18 of 22) and 82.0% (963 of 1,175), respectively, for the combination of imaging modalities and PSA. CONCLUSION While FDG-PET alone is insufficient, whole-body cancer screening with selected modalities including FDG-PET has initial performance supporting possible utility by detecting a wide variety of early-stage cancers with reasonable sensitivity. However, the detection of many indolent cancers and false positives necessitate continuing study for appropriate evaluation.

Cerebral circulation and metabolism in adults' Moyamoya disease-PET study

SummaryRegional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral metabolic rate for oxygen (rCMRO2) and cerebral blood volume (rCBV) in nine cases of moyamoya disease in adults were studied with positron emission CT (PET) scan, using15O steady-state methods. Three cases showed ischaemic symptoms and the other six cases showed haemorrhagic symptoms. PET scan was performed during the chronic stage. Control data were obtained from eight normal volunteers. Regional cerebral blood flow and other physiological parameters in cerebral gray matter, white matter and basal ganglia were compared with normal controls.All nine cases of Moyamoya disease showed decreased rCBF, though not significant, in cerebral gray matter, white matter and basal ganglia. Reduction of rCBF was significant in the cerebral cortex of six haemorrhagic cases. This significant decrease was considered to be due to diaschisis and also brain atrophy caused by the cerebral haemorrhage. There was a significant increase in rCBV in white matter of the both ischaemic and haemorrhagic cases. The calculated value of CBF/CBV is considered to be an index of perfusion pressure. This value was significantly decreased in all three regions, though rOEF was not significantly increased in moyamoya disease. Hence the cerebral circulation in adults with moyamoya disease appears to be characterized by a mild decrease in perfusion pressure and prolonged circulated time.

Incidence and characteristics of uterine leiomyomas with FDG uptake

ObjectiveUterine leiomyomas sometimes show focal 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images that may result in a false-positive diagnosis for malignant lesions. This study was conducted to investigate the incidence and characteristics of uterine leiomyomas that showed FDG uptake.MethodsWe reviewed FDG-PET and pelvic magnetic resonance (MR) images of 477 pre-menopausal (pre-MP, age 42.1 ± 7.3 years) and 880 post-MP (age 59.9 ± 6.8 years) healthy women who underwent these tests as parts of cancer screening. Of 1357, 323 underwent annual cancer screening four times, 97 did three times, 191 did twice, and the rest were screened once. Focal FDG uptake (maximal standardized uptake value > 3.0) in the pelvis was localized and characterized on co-registered PET/MR images.ResultsUterine leiomyomas were found in 164 pre-MP and 338 post-MP women. FDG uptake was observed in 18 leiomyomas of 17 of the 164 (10.4%) pre-MP women and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP women. The incidence was significantly higher in pre-MP women than in post-MP women (chi-square, P < 0.001). Of the 22, 13 showed signal intensity equal to or higher than that of the myometrium on T2-weighted MR images, which suggested abundant cellularity, whereas the majority of leiomyomas without FDG uptake showed low signal intensity. Of the 13 women, 12 examined more than twice showed substantial changes in the level of FDG uptake in leiomyomas each year with FDG uptake disappearing or newly appearing. These changes were observed frequently in relation with menopause or menstrual phases.ConclusionsLeiomyomas with focal FDG uptake were seen in both pre-and post-MP women with a higher incidence in pre-MP women. Abundant cellularity and hormonal dependency may explain a part of the mechanisms of FDG uptake in leiomyomas. It is important to know that the level of FDG uptake in leiomyomas can change and newly appearing FDG uptake does not necessarily mean malignant transformation.

Uncoupling of Oxygen and Glucose Metabolism in Persistent Crossed Cerebellar Diaschisis

BACKGROUND AND PURPOSE The pathophysiology of deafferentation-induced changes after stroke remains unclear. Some supratentorial strokes cause persistent decreases in blood flow and metabolism in the contralateral cerebellum (persistent crossed cerebellar diaschisis[CCD]). Our previous study showed uncoupling of oxygen consumption and blood flow in this condition, which may reflect a characteristic change in brain metabolism caused by deafferentation. This uncoupling might be related to oxidation of some substrates other than blood-borne glucose, which could also lead to the uncoupling of oxygen consumption and glucose utilization. The purpose of this study was to investigate whether oxygen consumption is uncoupled from glucose utilization in persistent CCD. METHODS Using positron emission tomography in 10 unilateral supratentorial stroke patients, we evaluated regional blood flow, oxygen consumption, and glucose utilization in the cerebellar cortex in the chronic stage. Eight patients with a significant cerebellar blood flow asymmetry, defined as outside the 95% confidence limits predefined in 9 normal subjects, were selected as patients with persistent CCD. RESULTS In patients with CCD, the cerebellar cortex contralateral to the stroke showed significant decreases in both oxygen consumption and glucose utilization compared with the ipsilateral cerebellar cortex. The decrease in oxygen consumption was less than the decrease in glucose utilization, resulting in a significant increase in the oxygen consumption/glucose utilization ratio. CONCLUSIONS Persistent CCD caused by stroke may induce uncoupling of oxygen consumption and glucose utilization, which may reflect a characteristic change in brain metabolism caused by deafferentation.