Positron emission tomography/computed tomography as a clinical diagnostic tool for anterior mediastinal tumors.

PURPOSE: The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. METHODS: A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17-84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. RESULTS: Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin's lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. CONCLUSION: Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

A longitudinal study of the relationship between personality traits and the annual rate of volume changes in regional gray matter in healthy adults.

To investigate whether personality traits affect the rate of decline of gray matter volume, we analyzed the relationships between personality traits and the annual rate of changes of gray matter volume in 274 healthy community dwelling subjects with a large age range by applying a longitudinal design over 6 years, using brain magnetic resonance images (MRI) and the Revised NEO Personality Inventory (NEO-PI-R) at baseline. Brain MRI data were processed using voxel-based morphometry with a custom template by applying the DARTEL diffeomorphic registration tool. For each subject, we used NEO-PI-R to evaluate the five major personality traits, including neuroticism, extraversion, openness, agreeableness, and conscientiousness. The results show that the annual rate of change in regional gray matter volume in the right inferior parietal lobule was correlated significantly and negatively with a personality of openness, which is known to be related to intellect, intellectual curiosity, and creativity adjusting for age, gender, and intracranial volume. This result indicates that subjects with a personality trait of less openness have an accelerated loss of gray matter volume in the right inferior parietal lobule, compared with subjects with a personality trait of more openness. Because the right inferior parietal lobule is involved in higher cognitive function such as working memory and creativity, a personality trait of openness is thought to be important for preserving gray matter volume and cognitive function of the right inferior parietal lobule in healthy adults.

A longitudinal study of age- and gender-related annual rate of volume changes in regional gray matter in healthy adults.

The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community-dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age-by-gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging.

Correlation between high-sensitivity C-reactive protein and brain gray matter volume in healthy elderly subjects.

Although elevated serum high-sensitivity C-reactive protein (hsCRP) is related to atherosclerosis, brain infarction, and cognitive decline, it has not been clarified whether increased hsCRP is associated with the decline in brain gray matter volume. Therefore, the purpose of this study was to determine the relationship between hsCRP levels and brain regional gray matter volume using brain magnetic resonance imaging (MRI) data from 109 community-dwelling healthy elderly subjects. Brain MRIs were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra (DARTEL) procedure. We found a significant negative correlation between regional gray matter volume of the posterior and lateral aspects of the left temporal cortex and hsCRP level after adjusting for age, gender, and intracranial volume. Our results suggest that subjects who have mild inflammation related to arteriosclerosis have decreased regional gray matter volume in the posterior and lateral aspects of the left temporal cortex. Thus, preventing the progression of arteriosclerosis may be important for preventing a decrease in gray matter volume in healthy elderly subjects.

Correlation between pulmonary function and brain volume in healthy elderly subjects.

INTRODUCTION: Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. METHODS: Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. RESULTS: We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. CONCLUSION: Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Age-related changes in topological organization of structural brain networks in healthy individuals.

The aim of this study was to examine structural brain networks using regional gray matter volume, as well as to investigate changes in small-world and modular organization with normal aging. We constructed structural brain networks composed of 90 regions in young, middle, and old age groups. We randomly selected 350 healthy subjects for each group from a Japanese magnetic resonance image database. Structural brain networks in three age groups showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection cost. The small-world efficiency and node betweenness varied significantly and revealed a U- or inverted U-curve model tendency among three age groups. Results also demonstrated that structural brain networks exhibited a modular organization in which the connections between regions are much denser within modules than between them. The modular organization of structural brain networks was similar between the young and middle age groups, but quite different from the old group. In particular, the old group showed a notable decrease in the connector ratio and the intermodule connections. Combining the results of small-world efficiency, node betweenness and modular organization, we concluded that the brain network changed slightly, developing into a more distributed organization from young to middle age. The organization eventually altered greatly, shifting to a more localized organization in old age. Our findings provided quantitative insights into topological principles of structural brain networks and changes related to normal aging.

Correlation between baseline regional gray matter volume and global gray matter volume decline rate.

Evaluating whole-brain or global gray matter volume decline rate is important in distinguishing neurodegenerative diseases from normal aging and in anticipating cognitive decline over a given period in non-demented subjects. Whether a significant negative correlation exists between baseline regional gray matter volume of several regions and global gray matter volume decline in the subsequent time period in healthy subjects has not yet been clarified. Therefore, we analyzed the correlation between baseline regional gray matter volumes and the rate of global gray matter volume decline in the period following baseline using magnetic resonance images of the brains of 381 healthy subjects by applying a longitudinal design over 6 years using voxel-based morphometry. As a result, the annual percentage change in gray matter ratio (GMR, APC(GMR)), in which GMR represents the percentage of gray matter volume in the intracranial volume, showed a significant negative correlation with the baseline regional gray matter volumes of the right posterior cingulate cortex/precuneus and the left hippocampus. Additionally, baseline regional gray matter volume of both the right PCC/precuneus and the left hippocampus significantly distinguished whether the APC(GMR) was above or below the mean of APC(GMR). Our results suggest that baseline regional gray matter volume predicts the rate of global gray matter volume decline in the subsequent period in healthy subjects. Our study may contribute to distinguishing neurodegenerative diseases from normal aging and to predicting cognitive decline.

Correlation between gray/white matter volume and cognition in healthy elderly people.

This study applied volumetric analysis and voxel-based morphometry (VBM) of brain magnetic resonance (MR) images to assess whether correlations exist between global and regional gray/white matter volume and the cognitive functions of semantic memory and short-term memory, which are relatively well preserved with aging, using MR image data from 109 community-dwelling healthy elderly individuals. We used the Information and Digit Span subtests of the Wechsler Adult Intelligent Scale-Revised as measures of semantic memory and short-term memory, respectively. We found significant positive correlations between the gray matter ratio, the percentage of gray matter volume in the intracranial volume, and performance on the Digit Span subtest, and between the regional gray matter volumes of the bilateral anterior temporal lobes and performance on the Information subtest. No significant correlations between performance on the cognitive tests and white matter volume were found. Our results suggest that individual variability in specific cognitive functions that are relatively well preserved with aging is accounted for by the variability of gray matter volume in healthy elderly subjects.

Correlation between degree of white matter hyperintensities and global gray matter volume decline rate.

INTRODUCTION: Whether the degree of white matter hyperintensities (WMHs) shows a significant correlation with the rate of global gray matter volume decline over a period following initial baseline measurement remains unclear. The purpose of the present study was to reveal the relationship between the degree of WMHs at baseline and the rate of global gray matter volume decline by applying a longitudinal design. METHODS: Using a 6-year longitudinal design and magnetic resonance images of the brains of 160 healthy individuals aged over 50 years and living in the community, we analyzed the correlation between degree of WMHs using Fazekas scaling at baseline and rate of global gray matter volume decline 6 years later. To obtain the rate of global gray matter volume decline, we calculated global gray matter volume and intracranial volume at baseline and at follow-up using a fully automated method. RESULTS: The annual percentage change in the gray matter ratio (GMR, APC(GMR)), in which GMR represents the percentage of gray matter volume in the intracranial volume, showed a significant positive correlation with the degree of deep WMHs and periventricular WMHs at baseline, after adjusting for age, gender, present history of hypertension, and diabetes mellitus. CONCLUSION: Our results suggest that degree of WMHs at baseline predicts the rate of gray matter volume decline 6 years later and that simple visual scaling of WMHs could contribute to predicting the rate of global gray matter volume decline.

(18)FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases.

OBJECTIVE: The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased (18)F-fluorodeoxy-D: -glucose ((18)FDG) uptake. Though the possible utility of (18)FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung (18)FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between (18)FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD. METHODS: Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from (18)FDG-PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and (18)FDG uptake between the control and ILD cases were tested. RESULTS: The CT density and (18)FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases. CONCLUSIONS: Lung (18)FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung (18)FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases.

Increase of serum CA19-9 level without an evident lesion on conventional imaging is insufficient for justification of 18FDG-PET examination.

BACKGROUND/AIMS: The serum tumor marker carbohydrate associated antigen 19-9 (CA19-9) has been used for screening for cancer, because its increase has been associated with many cancers. We aimed to evaluate the clinical value of positron emission tomography using F-18 fluorodeoxyglucose (18FDG-PET) that was prompted by increases of serum CA19-9 without findings on conventional imaging. METHODOLOGY: Twenty-two patients were retrospectively selected. Eleven were without a history of cancer and eleven had a history of cancer and were treated with curative intent. All 18FDG-PET findings were compared with the findings of histopathology by surgery or biopsy, or clinical follow-up for at least 1 year. RESULTS: We found only two true positive cases, and eleven cases without a cancer history included 10 true negatives and one false positive. CONCLUSIONS: Increases in serum CA19-9 are caused by many benign conditions. Increases of CA19-9 without findings on conventional imaging do not justify 18FDG-PET examination, particularly in patients without a cancer history.

Diagnosing active inflammation in the SAPHO syndrome using 18FDG-PET/CT in suspected metastatic vertebral bone tumors.

The vertebral spine is frequently affected by the SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. We report the collective imaging findings of hybrid F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT), as well as bone scans and magnetic resonance imaging, in a patient who had suspected metastatic vertebral bone tumors. 18FDG-PET/CT can be utilized to exclude metastatic vertebral tumors, as well as identifying stable lesions, by demonstrating active inflammatory lesions with accurate anatomic localization through the convergence of the functional information from 18FDG uptake with the anatomic information of CT.

Predicting human performance by channelized Hotelling observer in discriminating between Alzheimer's dementia and controls using statistically processed brain perfusion SPECT.

OBJECTIVE: We compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer's disease (AD) from SPECT images. METHODS: The I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (lambda) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared. RESULTS: Among the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images. CONCLUSIONS: The performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer's dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry.

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.

Database of normal human cerebral blood flow measured by SPECT: II. Quantification of I-123-IMP studies with ARG method and effects of partial volume correction.

UNLABELLED: The limited spatial resolution of SPECT causes a partial volume effect (PVE) and can lead to the significant underestimation of regional tracer concentration in the small structures surrounded by a low tracer concentration, such as the cortical gray matter of an atrophied brain. The aim of the present study was to determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and without PVE correction (PVC), and to determine regional differences in the effect of PVC and their association with the regional tissue fraction of the brain. METHODS: Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy elderly subjects (18 males, 15 females, 54-74 years old) using the autoradiographic method. We corrected CBF for PVE using segmented MR images, and analyzed quantitative CBF and regional differences in the effect of PVC using tissue fractions of gray matter (GM) and white matter (WM) in regions of interest (ROIs) placed on the cortical and subcortical GM regions and deep WM regions. RESULTS: The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9 +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively. There were statistically significant differences in the effect of PVC among ROIs, but not between genders. The effect of PVC was small in the cerebellum and parahippocampal gyrus, and it was large in the superior frontal gyrus, superior parietal lobule and precentral gyrus. CONCLUSION: Quantitative CBF in GM recovered significantly, but did not reach values as high as those obtained by invasive methods or in the H2(15)O PET study that used PVC. There were significant regional differences in the effect of PVC, which were considered to result from regional differences in GM tissue fraction, which is more reduced in the frontoparietal regions in the atrophied brain of the elderly.

Diffuse bone marrow uptake on F-18 FDG PET in patients with myelodysplastic syndromes.

It is well known that hematopoietic cytokine stimulation can cause diffuse increase of FDG accumulation in bone marrow on PET imaging, which simulates that seen in patients with bone marrow metastases. However, diffuse bone marrow FDG uptake can be caused by other etiologies. We report 2 patients who did not have a history of hematopoietic cytokine stimulation. The FDG PET images showed diffuse bone marrow FDG uptake, and the patients were diagnosed as having myelodysplastic syndromes. These cases demonstrate that diffuse FDG uptake by bone marrow can suggest neoplastic disease of the hematopoietic tissues.

Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry.

BACKGROUND: The brain morphological changes in subthreshold depression (sD) have not been clarified. We examined the structural difference in regional gray matter volume between community-dwelling elderly subjects with sD and age-matched nondepressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging (MRI). METHODS: Thirty-four community-dwelling elderly subjects with sD and 109 age-matched nondepressed normal subjects were studied by MRI. We defined subjects with sD as those who showed a Geriatric Depression Scale score of 15 or higher and a Mini Mental State Examination score of 22 or higher, and do not fulfill the criteria of major depressive disorder (MDD) in the Diagnostic and Statistical Manual for Mental Disorders IV. We collected brain magnetic resonance images of 34 subjects with sD and 109 age-matched normal subjects, and analyzed the difference in regional gray matter volume between these two groups by VBM. RESULTS: Male subjects with sD had significantly smaller volumes of the medial part of the bilateral frontal lobes and the right precentral gyrus than normal male subjects. LIMITATIONS: We have not clarified the discrepancy in the results of gender difference. CONCLUSIONS: Our study revealed that even community-dwelling elderly male subjects with sD show bilateral prefrontal gray matter volume reduction, which was reported to be observed in elderly patients with MDD, although there is no significant volume reduction in the hippocampus, which was also reported to be observed in MDD. Our study may contribute to clarifying the mechanism underlying brain pathological changes in sD.

Apparent CBF decrease with normal aging due to partial volume effects: MR-based partial volume correction on CBF SPECT.

Several studies using single photon emission tomography (SPECT) have shown changes in cerebral blood flow (CBF) with age, which were associated with partial volume effects by some authors. Some studies have also demonstrated gender-related differences in CBF. The present study aimed to examine age and gender effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a SPECT scanner, before and after partial volume correction (PVC) using magnetic resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was segmented to yield grey and white matter images and coregistered to a corresponding SPECT image, followed by convolution to approximate the SPECT spatial resolution. PVC-SPECT images were produced using the convoluted grey matter MR (GM-MR) and white matter MR images. The age and gender effects were assessed using SPM99. Decreases with age were detected in the anterolateral prefrontal cortex and in areas along the lateral sulcus and the lateral ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC-SPECT images, decreases in CBF in the lateral prefrontal cortex lost their statistical significance. Decreases in CBF with age found along the lateral sulcus and the lateral ventricle, on the other hand, remained statistically significant, but observation of the spatially normalized MR images suggests that these findings are associated with the dilatation of the lateral sulcus and lateral ventricle, which was not completely compensated for by the spatial normalization procedure. Our present study demonstrated that age effects on CBF in healthy subjects could reflect morphological differences with age in grey matter.

Effects of tissue heterogeneity on cerebral vascular response to acetazolamide stress measured by an I-123-IMP autoradiographic method with single-photon emission computed tomography.

OBJECTIVES: Single-photon emission computed tomography (SPECT) with iodine-123 (123I)-labeled N-isopropyl-p-iodoamphetamine (IMP) is widely used in measuring the cerebral blood flow (CBF) response to acetazolamide stress for assessment of cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an autoradiographic (ARG) method has been developed and is widely used. Because the relation between the brain counts on the SPECT scan and CBF is not linear in the ARG method, a mixture of gray and white matter in a pixel causes errors in the calculation of CBF. In the present study, errors in the calculation of CBF and vascular response to acetazolamide stress by the ARG method due to tissue heterogeneity were estimated by simulation study. Correction for effects of tissue heterogeneity in SPECT data was also attempted. METHODS: Images of gray and white matter fraction were obtained by voxel-based morphometry analysis of magnetic resonance (MR) imaging data set. Ideal CBF images, which were generated from gray and white matter fraction images with assumed blood flow values for gray and white matter, were compared to CBF images generated by the ARG method. Correction for effects of tissue heterogeneity in SPECT data was performed with gray and white matter fraction data obtained from MR images. RESULTS: Systematic underestimation of CBF due to tissue heterogeneity was observed in all brain regions. In the neocortical regions, underestimation by -21% to -16%, -26% to -20%, -31% to -24%, and -35% to -27% was observed for gray and white matter blood flow of 80 and 20, 100 and 25, 120 and 30, and 140 and 35 ml/100 ml/min, respectively. Vascular response was also systematically underestimated in most brain regions. Vascular responses in the neocortical regions ranged from 17% to 20%, from 31% to 37%, and from 42% to 52% when ideal vascular responses were 25%, 50%, and 75%, respectively. After correction for the effects of tissue heterogeneity, values of vascular response to acetazolamide stress ranged from 64% to 116% in the neocortical regions, whereas values obtained by the ARG method ranged from 48% to 52%. CONCLUSION: Underestimation of the vascular response to acetazolamide stress due to tissue heterogeneity should be considered in the estimation of cerebral vascular reserve.

Voxel-based morphometry of human brain with age and cerebrovascular risk factors.

The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter.