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Correction for Partial-Volume Effects on Brain Perfusion SPECT in Healthy Men

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Correction for Partial-Volume Effects on Brain Perfusion SPECT in Healthy Men Correction for Partial-Volume Effects on Brain Perfusion SPECT in Healthy Men Hiroshi Matsuda, MD1; Takashi Ohnishi, MD1; Takashi Asada, MD2; Zhi-jie Li, MD1,3; Hidekazu Kanetaka, MD1; Etsuko Imabayashi, MD1; Fumiko Tanaka, MD1; and Seigo Nakano, MD4 1Department of Radiology, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan; 2Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan; 3Department of Nuclear Medicine, The Second Clinical Hospital of China Medical University, Shen-Yang City, China; and 4Department of Geriatric Medicine, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan The limited spatial resolution of SPECT scanners does not allow Functional changes in the brains of healthy elderly people an exact measurement of the local radiotracer concentration in and patients with neurodegenerative disorders have been brain tissue because partial-volume effects (PVEs) underesti- studied widely by SPECT. However, due to the limited mate concentration in small structures of the brain. The aim of this study was to determine which brain structures show greater spatial resolution of SPECT, the accurate measurement of influence of PVEs in SPECT studies on healthy volunteers and to tracer concentration in brain structures depends on several investigate aging effects on SPECT after the PVE correction. physical limitations—particularly, the relation between ob- Methods: Brain perfusion SPECT using 99mTc-ethylcysteinate ject size and scanner spatial resolution. This relation, known dimer was performed in 52 healthy men, 18–86 y old. The as the partial-volume effect (PVE), biases the measured regional cerebral blood flow (rCBF) was noninvasively measured concentration in small structures by diminishing the true using graphical analysis. SPECT images were corrected for PVEs using gray-matter volume, which was segmented from concentration. The PVE causes a volume-averaging effect coregistered MR images and convoluted with spatial resolution between the tissue elements of gray matter, white matter, of SPECT scanners. Absolute rCBF data were measured using and cerebrospinal fluid in a region of brain. a 3-dimensional (3D) stereotactic template for regions of interest Recently, the high-resolution anatomic detail available on anatomically standardized SPECT. We examined correlation with MRI techniques has led to the development of MR- of advancing age with rCBF before and after the PVE correction. based methods to correct PET or SPECT data for PVEs To validate the correction method for PVEs, a Hoffman 3D brain phantom experiment was also performed. Results: The PVE (1–5). We have already applied this approach to determine correction remarkably reduced the coefficient of variation for which brain structures show the greatest influence of PVEs SPECT counts in the whole phantom. The PVE correction made in SPECT studies on Alzheimer’s disease (5). The aim of the rCBF distribution more homogeneous throughout the brain this study was to determine which brain structures show the with less intersubject variation than the original distribution. greatest influence of PVEs in SPECT studies in healthy men There were significant negative correlations between age and adjusted rCBF in the bilateral perisylvian and medial frontal and to investigate aging effects on brain perfusion SPECT areas. These correlations remained significant after the PVE before and after correction for PVEs. correction. Instead of a positive correlation in the medial tem- poral structures between age and adjusted rCBF before the PVE correction, the sensorimotor and parietal areas mainly showed MATERIALS AND METHODS positive correlations after the correction. Conclusion: SPECT data reflect both brain volume loss and functional changes. Use Subjects Ϯ of the PVE correction in brain perfusion SPECT provides a more The subjects were 52 healthy men, 18–86 y old (mean SD, accurate determination of rCBF even in healthy volunteers. 58.4 Ϯ 20.5 y). Their performance was within normal limits on Key Words: SPECT; MRI; partial-volume effects; aging; statis- both the Wechsler Memory Scale-Revised (6) and the Wechsler tical parametric mapping Adult Intelligence Scale-Revised (7). The Mini-Mental State Ex- Ͼ J Nucl Med 2003; 44:1243–1252 amination score (8) for subjects 55 y old ranged from 26 to 30 (mean Ϯ SD, 28.6 Ϯ 1.4). All subjects were right-handed and were screened by questionnaire and medical history to exclude those with medical problems potentially affecting the central nervous system. In addition, none of them had asymptomatic cerebral Received Dec. 13, 2002; revision accepted Mar. 28, 2003. For correspondence or reprints contact: Hiroshi Matsuda, MD, Department infarction detected by T2-weighted MRI. The Ethics Committee of of Radiology, National Center Hospital for Mental, Nervous, and Muscular the National Center of Neurology and Psychiatry approved this Disorders, National Center of Neurology and Psychiatry, 4-1-1, Ogawahi- gashi, Kodaira, 187-8551, Tokyo, Japan. study for healthy volunteers, all of whom gave informed consent to E-mail: [email protected] participate. PARTIAL-VOLUME EFFECTS ON BRAIN SPECT • Matsuda et al. 1243 Global and Regional CBF Measurements Gaertner et al. (1) and Labbe et al. (2). A three-dimensional (3D) Before SPECT was performed, an intravenous line was estab- volumetric acquisition of a T1-weighted gradient-echo sequence lished in all subjects. They were injected, while lying down in the produced a gapless series of thin sagittal sections using a magne- supine position with eyes closed in a dimly lit, quiet room. Each tization preparation rapid acquisition gradient-echo sequence received a 600-MBq intravenous injection of 99mTc-ethylcysteinate (echo time/repetition time, 4.4/11.4; flip angle, 15°; acquisition dimer (99mTc-ECD). The global CBF was noninvasively measured matrix, 256 ϫ 256; slices thickness, 1.23 mm). The acquired MR using graphical analysis, as has been described in reports without images were reformatted to gapless 2-mm-thick transaxial images. any blood sampling (9). The passage of the tracer from the aortic MR images were then converted to the same isometric matrix size arch to the brain was monitored in a 128 ϫ 128 format for 100 s as that for SPECT images using ANALYZE. SPM99 then seg- at l-s intervals using a rectangular gamma camera with a parallel- mented these isometric MR images into gray matter, white matter, hole collimator on a triple-head SPECT system (Multispect3; cerebrospinal fluid, and other compartments. The segmentation Siemens Medical Systems, Inc.). Regions of interest (ROIs) were procedure involves calculating for each voxel a Bayesian proba- hand-drawn over the aortic arch (ROIaorta) and both brain hemi- bility of belonging to each tissue class based on a priori MRI spheres (ROIbrain). A hemispheric brain perfusion index (BPI) was information with inhomogeneity correction for magnetic field (13). determined as follows before the start of the initial backdiffusion The AIR software was used to align the SPECT to the MRI scans of the tracer from brain to blood (9): of each subject using a 6-parameter rigid-body transformation as described by Ibanez et al. (4). Before coregistration of SPECT and ⅐ 10 ROIaorta size BPI ϭ 100 ⅐ ku , Eq. 1 MRI, the outer scalp was removed from MRI by applying a binary ROIbrain size mask for the whole brain (mentioned later) to the MRI. A 3D convolution with the point spread function of the SPECT device where ku is the unidirectional influx rate for the tracer from blood (assumed to be a simple 3D gaussian with full width at half to brain, which is determined by the slope of the line in graphical maximum [FWHM] of 9.0 ϫ 9.0 ϫ 9.0 mm) was performed to analysis within the first 30 s after injection. ROI size and aorta obtain coefficients of dispersion for each voxel as also described ROI size are the drawn sizes of ROI for aorta and brain, brain by Ibanez et al. (4). This procedure of identification of spatial respectively. Then, the BPI was converted to global cerebral blood resolution between gray-matter SPECT and MR images makes it flow (CBF) values using the following regression equation ob- possible to correct PVEs by division of these 2 images in the final tained from previous 133Xe inhalation studies (9): procedure. These convoluted gray-matter and white-matter images global CBF ϭ 2.6 ϫ BPI ϩ 19.8. Eq. 2 were normalized to have a maximum count of 1.0 as 32-bit real values. A binary volume image was created from this convoluted Ten minutes after the injection of 99mTc-ECD, brain SPECT was gray-matter image with the threshold set to 35% of the maximum performed using cameras equipped with high-resolution fanbeam value as a mask image for gray matter. A mask image for the collimators. For each camera, projection data were obtained in a whole brain was created from this mask image for gray matter by 128 ϫ 128 format for 24 angles of 120° at 50 s per angle. A Shepp filling the interior holes in the brain. White- matter SPECT images and Logan Hanning filter was used as a filtered backprojection were then simulated from these normalized white-matter MR method for SPECT image reconstruction at 0.7 cycle/cm. Attenu- images with convolution as follows. The maximum count of 1.0 ation correction was performed using Chang’s method with an for the normalized white-matter MR image was replaced by the Ϫ optimized effective attenuation coefficient of 0.09 cm 1.Tocal- maximum SPECT count in the white matter. To get the maximum culate regional CBF (rCBF) and to correct for incomplete retention count for the white matter of SPECT, an ROI was automatically 99m of Tc-ECD in the brain, the following linearization algorithm determined by setting the threshold to Ͼ95% of the maximum (10) of the curvilinear relationship between brain activity and count density of the white-matter MR images.
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