Multimodal analysis using [11C]PiB-PET/MRI for functional evaluation of patients with Alzheimer's disease.

BACKGROUND: Multimodal PET/MRI image data simultaneously obtained from patients with early-stage of Alzheimer's disease (eAD) were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain. Fifty-eight patients with mild cognitive impairment and early dementia (29 males, 69 ± 12 years) underwent [11C]Pittsburgh compound-B (PiB) PET/MRI with 70-min PET and MRI scans. Sixteen age-matched healthy controls (CTL) (9 males, 68 ± 11 years) were also studied with the same scanning protocol. Cerebral blood flow (CBF) was calculated from the early phase PET images using the image-derived input function method. A standardized uptake value ratio (SUVr) was calculated from 50 to 70 min PET data with a reference region of the cerebellar cortex. MR images such as 3D-T1WI, resting-state functional MRI (RS-fMRI), diffusion tensor image (DTI), and perfusion MRI acquired during the dynamic PET scan were also analyzed to evaluate various brain functions on MRI. RESULTS: Twenty-seven of the 58 patients were determined as eAD based on the results of PiB-PET and clinical findings, and a total of 43 subjects' data including CTL were analyzed in this study. PiB SUVr values in all cortical regions of eAD were significantly greater than those of CTL. The PiB accumulation intensity was negatively correlated with cognitive scores. The regional PET-CBF values of eAD were significantly lower in the bilateral parietal lobes and right temporal lobe compared with CTL, but not in MRI perfusion; however, SPM showed regional differences on both PET- and MRI-CBF. SPM analysis of RS-fMRI delineated regional differences between the groups in the anterior cingulate cortex and the left precuneus. VBM analysis showed atrophic changes in the AD group in a part of the bilateral hippocampus; however, analysis of fractional anisotropy calculated from DTI data did not show differences between the two groups. CONCLUSION: Multimodal analysis conducted with various image data from PiB-PET/MRI scans showed differences in regional CBF, cortical volume, and neuronal networks in different regions, indicating that pathophysiologic and functional changes in the AD brain can be observed from various aspects of neurophysiologic parameters. Application of multimodal brain images using PET/MRI would be ideal for investigating pathophysiologic changes in patients with dementia and other neurodegenerative diseases.

Different distribution of (62) Cu ATSM and (18)F-FDG in head and neck cancers.

PURPOSE: [6²Cu]-diacetyl-bis(N4-methlythiosemicarbazone) (Cu-ATSM) was used to delineate hypoxic tissue in head-and-neck cancer, and its distribution was compared with that of ¹8F-FDG. MATERIALS AND METHODS: Thirty patients with head-and-neck cancer underwent Cu-ATSM and FDG PET within a 1 week interval. Accumulation of tracer for each PET image was converted to SUV. After coregisteration of PET images with individual anatomic images, multiple small ROIs were drawn on the tumor mass and applied to both PET images. SUV values were obtained for all ROIs (SUV(roi)), and the SUV(roi) regression lines between Cu-ATSM and FDG of each tumor were determined. RESULTS: The SUV mean of Cu-ATSM was lower than that of FDG for both squamous cell carcinoma (SCC) and adenocarcinoma (P < 0.05). In 27 patients with SCC, Cu-ATSM accumulated higher in the peripheral region than in the center of the tumor, and FDG showed the other tendency. Thus, the relationship of the SUV(roi) for Cu-ATSM and FDG showed a negative correlation in SCC. However, 3 adenocarcinoma cases showed similar and homogenous accumulation in the tumor mass with a positive SUV(roi) correlation for the 2 tracers. The regression slope means were -0.12 ± 0.08 for SCC (n = 27) and 0.28 ± 0.12 (n = 3) for adenocarcinoma. CONCLUSION: In patients with head-and-neck cancer, intratumoral distribution of Cu-ATSM and FDG showed a negative correlation in SCC and a positive correlation in adenocarcinoma. The 2 tracers represented different pathophysiological microenvironments in different tumors, suggesting that noninvasive hypoxic tissue imaging with Cu-ATSM would be beneficial in the pretreatment evaluation of head-and-neck cancer.

Appropriate parameters of the ordered-subset expectation maximization algorithm on measurement of myocardial blood flow and oxygen consumption with 11C-acetate PET.

OBJECTIVE: The purpose of this study was to evaluate the appropriate parameters of a filter and of subsets (S) and iterations (I) of the ordered-subset expectation maximization (OSEM) algorithm in 11C-acetate PET. METHODS: A Hanning filter (HF) and a Gaussian filter (GF) were selected for filtered back-projection (FBP) and the OSEM algorithm, respectively. After evaluation of the optimal HF size, the GF size was optimized using healthy volunteers (HV). Myocardial blood flow (MBF) and oxygen consumption (k(mono)) values were calculated by combining 4S, 16S, or 28S with 2I, 4I, 6I, or 8I of the OSEM (MBF(OSEM) and k(monoOSEM), respectively) in eight HV and eight coronary artery disease (CAD) patients. These MBF(OSEM) and k(monoOSEM) values were compared with those obtained using FBP (MBF(FBP) and k(monoFBP), respectively). RESULTS: Optimal HF and GF (10.0GF) sizes for the FBP and OSEM algorithms, respectively, were 10.0 mm full-width resolution at half-maximum. MBF(OSEM) was changed by modifying the parameters of the OSEM algorithm. The best correlations were between MBF(FBP) and MBF(OSEM), with 28S6I and 10.0GF for HV patients and 28S8I for CAD patients. However, the MBF(OSEM) with 28S8I was significantly different from MBF(FBP) at the global myocardium in HV. The k(monoOSEM) with 28S6I was not significantly different from k(monoFBP) in HV or CAD patients. CONCLUSION: Appropriate parameters are 28S6I with a 10.0GF on the MBF(OSEM) and k(monoOSEM) measurement using 11C-acetate. Diagnostic performance will improve using noiseless, artifact-reduction images, and accurate quantitative values that are provided by the OSEM algorithm with the appropriate parameters.

Cerebral oxygen metabolism of rats using injectable (15)O-oxygen with a steady-state method.

To develop a less-stressful and simple method for measurement of the cerebral metabolic rate of oxygen (CMRO(2)) in small animals, the steady-state method was applied to injectable (15)O(2)-PET ((15)O(2)-positron emission tomography) using hemoglobin-containing vesicles ((15)O(2)-HbV). Ten normal rats and 10 with middle cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner. A series of (15)O-PET scans with C(15)O-labeled HbV, H(2)(15)O, and (15)O(2)-HbV were performed with 10 to 15 minutes intervals to measure cerebral blood volume (CBV), cerebral blood flow (CBF), and CMRO(2). Positron emission tomography scans were started with a tracer injection using a multiprogramming syringe pump, which provides a slowly increasing injection volume to achieve steady-state radioactivity for H(2)(15)O and (15)O(2)-HbV scans. The radioactivity concentration of (15)O rapidly achieved equilibrium in the blood and whole brain at about 2 minutes after H(2)(15)O and (15)O(2)-HbV administration, which was stable during the scans. The whole brain mean values of CBF, CBV, and CMRO(2) were 54.3±2.0 mL per 100 g per minute, 4.9±0.4 mL/100 g, and 2.8±0.2 µmoL per g per minute (6.2±0.4 mL per 100 g per minute) in the normal rats, respectively. In the MCAO model rats, all hemodynamic parameters of the infarction area on the occlusion side significantly decreased. The steady-state method with (15)O-labeled HbV is simple and useful to analyze hemodynamic changes in studies with model animals.

Feasibility of 62Cu-ATSM PET for evaluation of brain ischaemia and misery perfusion in patients with cerebrovascular disease.

PURPOSE: [(62)Cu]Diacetyl-bis(N (4)-methylthiosemicarbazone) ((62)Cu-ATSM) was used to evaluate brain haemodynamic impairment in patients with cerebrovascular disease (CVD) as a simplified evaluation method. The tracer distribution was compared with haemodynamic parameters obtained by (15)O positron emission tomography (PET). METHODS: Ten patients with major cerebral arterial occlusive disease (aged 66 ± 7 years) underwent PET with (62)Cu-ATSM and (15)O tracers ((15)O-water, (15)O(2) and C(15)O). Seven healthy volunteers also underwent (62)Cu-ATSM PET as normal controls. After the injection of (62)Cu-ATSM, 20-min dynamic PET data acquisition was started. Early- and delayed-phase images of (62)Cu-ATSM were obtained by averaging the initial 3-min and the last 10-min frame data, which were used for perfusion and retention images. Cerebral blood flow (CBF), blood volume, metabolic rate of oxygen (CMRO(2)) and oxygen extraction fraction (OEF) were measured by (15)O-gas and water studies and compared with early- and delayed-phase (62)Cu-ATSM images and delayed to early (D/E) ratio. Regional values were compared after all parametric images were coregistered to individual MRI. The asymmetry index (AI) was also calculated for OEF and Cu-ATSM D/E ratio, and diagnostic ability for detecting misery perfusion was compared. RESULTS: In the affected hemisphere of the patients, the mean values of haemodynamic parameters were CBF = 33.8 ± 5.9 ml/100 g per min, CMRO(2) = 2.6 ± 0.3 ml/100 g per min and OEF = 48 ± 7%. Standardized uptake values (SUVs) for (62)Cu-ATSM in early and delayed phases were 2.00 ± 0.13 and 1.04 ± 0.09 in the ipsilateral hemisphere and 2.13 ± 0.14 and 1.04 ± 0.08 in the contralateral hemisphere, respectively. The early-phase (62)Cu-ATSM images corresponded well to CBF images, and the D/E ratio images were similar to OEF images. Regional values obtained from D/E ratio images were significantly correlated with regional OEF. AIs of OEF and D/E ratio showed a significant correlation and diagnostic ability of misery perfusion was slightly better in AI of D/E ratio than that of OEF. CONCLUSION: Dynamic PET acquisition with (62)Cu-ATSM provided information on CBF distribution and local elevation of OEF in patients with chronic CVD. The findings of the present study showed the feasibility of the noninvasive molecular imaging method for diagnosing misery perfusion with a single venous tracer injection.

Development of an H(2)(15)O steady-state method combining a bolus and slow increasing injection with a multiprogramming syringe pump.

An (15)O-labeled water (H(2)(15)O) steady-state method for quantitative measurement of cerebral blood flow (CBF), which is less stressful to small animals with a few point blood sampling, was developed. After a simulation using a dose meter to achieve stable H(2)(15)O radioactivity in the blood with a multiprogramming syringe pump programmed for slowly increasing injection volume, 10 rats were studied with the injection method. Arterial blood was sampled every minute during 6-minute positron emission tomography (PET) scans. After the PET scan, N-isopropyl-p-[(125)I]-iodoamphetamine ((125)I-IMP) was injected into the same rat to measure CBF using the autoradiography method based on a microsphere model. Regions of interest were placed on the whole brain in H(2)(15)O-PET and (125)I-IMP-autoradiography images, and CBF values calculated from both methods were compared. Radioactivity in the dose meter achieved equilibrium ∼1 minute after starting the H(2)(15)O injection. In rat studies, radioactivity in the blood and brain rapidly achieved equilibrium at 2 minutes after administration. The correlation of CBF values of H(2)(15)O PET (49.2±5.4 mL per 100 g per minute) and those of (125)I-IMP autoradiography (49.1±5.2 mL per 100 g per minute) was excellent (y=1.01x-0.37, r(2)=0.97). The H(2)(15)O steady-state method with a continuously increasing injection is useful for CBF measurement in small animal studies, especially when multiple scans are required in the same animal.

[Effects of transmission scan protocol and attenuation correction method on normal database of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) brain positron emission tomography study].

Although post-injection transmission scan (POST-TS) after 2-[(18)F]fluoro-2-deoxy- D-glucose ((18)F-FDG) injection[A1] is useful for short examination times, the emission count of (18)F-FDG[A2] in the regional brain area was not completely subtracted with use of the POST-TS method. The purpose of this study was to investigate the effect of POST-TS and attenuation correction (AC) methods on the normal database (NDB). A 10 min pre-injection transmission scan (PRE-TS) was performed before (18)F-FDG[A3] was injected in eighteen normal volunteers. A 10 min POST-TS was then conducted beginning 40 min after (18)F-FDG[A4] injection, followed by a 10 min 2-dimentional emission scanning. To reconstruct each image of normal volunteers, the reconstruction was performed using the filtered back-projection (FBP) method and the ordered subsets expectation maximization (OSEM) method, with transmission-based measured attenuation correction (MAC) and the segmented attenuation correction (SAC) technique. Subtraction images of NDB with PRE-TS or POST-TS were evaluated using 3D-SSP. A phantom study was also performed in addition to a human study, and assessment was by region of interests and profile curves. NDB images with POST-TS were significantly lower in the bilateral frontal lobes and higher in the parietal lobes and occipital lobes, including the precuneus, than those with PRE-TS, regardless of the different AC and reconstruction algorithms. Therefore, we have to be careful to confirm not only emission scan methods and reconstruction algorithms, but also TS methods and AC methods in the NDB. It will be best to perform PET examinations using the same TS methods and AC methods between NDB and patients.