YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

Mutual effect of cerebral amyloid ß and peripheral lymphocytes in cognitively normal older individuals.

OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [11 C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aß deposition was quantified by cortical binding potential (PiB-BPND ). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB-BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. RESULTS: Subjects with high PiB-BPND showed significantly higher percentage of cytotoxic T cells (%CD3+ ). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB-BPND . Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB-BPND and vice versa. CONCLUSIONS: Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aß neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

High amyloid-ß deposition related to depressive symptoms in older individuals with normal cognition: a pilot study.

OBJECTIVE: Previous studies have reported depressive symptoms in the preclinical stages of Alzheimer's disease (AD). The objective of this study was to determine whether depressive symptoms are associated with cortical amyloid burden. In order to do this, we measured cortical amyloid via (11) C-labeled Pittsburgh Compound B ([(11) C]PIB) uptake using positron emission tomography (PET) in cognitively normal subjects. METHODS: We performed [(11) C]PIB-PET in 29 cognitively normal, older participants. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS). Aß deposition was quantified by binding potential (BPND ), and the association between cortical mean BPND values and GDS scores was evaluated. Analysis of parametric BPND images was performed to examine the relationship between regional BPND and GDS scores. RESULTS: We found a positive correlation between depressive symptoms and mean cortical PIB-BPND in groups of subjects with middle to high PIB-BPND . There was little change in GDS-depression score between subjects with low and middle PIB-BPND levels, while an increase in GDS was shown in the high PIB-BPND group. The main BPND increase was localized to the precuneus/posterior cingulate cortex (PCu/PCC) in subjects with high PIB-BPND , and we found a significant positive relationship between PIB-BPND in this area and depressive symptoms. CONCLUSIONS: Emotional dysregulation because of Aß neuropathology in the PCu/PCC may relate to depressive symptoms. More specifically, we found that older, cognitively normal patients with depressive episodes were more likely to have underlying AD pathology. Thus, depressive symptoms may increase the predictive ability of the identification of future AD cases. Copyright © 2016 John Wiley & Sons, Ltd.

The Effects of Misalignment between PET and CT Scans on Brain PET Study Using CT-based Attenuation Correction: A Phantom Study.

PURPOSE: The aim of this study was to evaluate the effects of inaccurate attenuation correction due to the misalignment between the computed tomography (CT)-based µ-map and the positron emission tomography (PET) data on a brain PET. METHODS: CT and PET scans were performed on a 3-dimension (3D) brain phantom, in which the grey matter region was filled with 18F-fluorodeoxyglucose (18F-FDG), and the skull region was filled with/without the bone-equivalent solution. The shifted PET images relative to the CT image were generated by the software-based translation of PET data in the cephalad/caudal and right directions, with a magnitude of the shift up to 30 mm and a step size of 5 mm. The regions of interest (ROIs) were drawn on the areas of the temporal lobes, parietal lobes, thalami, and cerebellums in the no-shifted image (reference). For each ROI, the radioactivity concentrations in the shifted images were compared with those of the reference. RESULTS: The errors in the radioactivity concentrations were increased with the increasing magnitude of the shift in all brain regions except for thalamus. For a 5 mm shift in the right direction, ± 10% errors were observed in the left/right temporal lobes. The accuracy of the radioactivity concentration in the temporal lobe was very sensitive to misalignment in the right directions. CONCLUSION: The misalignment between CT-based µ-map and PET data had larger effects on the surface regions of the brain rather than on deep brain structures.

Low amyloid-ß deposition correlates with high education in cognitively normal older adults: a pilot study.

OBJECTIVE: Several epidemiological studies have found a lower incidence of Alzheimer's disease in highly educated populations, but the protective mechanism of education against the disease is still unclear. Our objective was to investigate the association between education and (11) C-labeled Pittsburgh Compound B (PIB) uptake with positron emission tomography in participants with normal cognitive ability. METHODS: We performed (11) C-labeled PIB positron emission tomography and neuropsychological testing in 30 cognitively normal older participants. Of the participants, 16 had a period of education less than 12 years (low-education group) and 14 had more than 13 years (high-education group). Amyloid-ß deposition was quantified by binding potential (BPND ) in several brain regions and was compared between the groups with different education levels. RESULTS: We found significantly higher cortical PIB-BPND in the cognitively normal participants with low education compared with the ones with high education. None of the brain regions in low-education group showed significantly lower BPND values. This finding was not affected by the inclusion of possible confounding variables such as age, sex, and general intelligence. Our findings indicated a reduced amyloid pathology in highly educated, cognitively normal, participants. CONCLUSIONS: Our findings lead to the proposal that early-life education has a negative association with Alzheimer's disease pathology. This proposal is not in opposition to the brain reserve hypothesis. People with more education might be prone to a greater inhibitory effect against amyloid-ß deposition before the preclinical stage. At the same time, they have a greater reserve capacity, and greater pathological changes are required for dementia to manifest.

Determination of the Clostridium perfringens-binding site on fibronectin.

The extracellular matrix protein fibronectin (Fn) is known to bind to the surface of Clostridium perfringens cells. Fn is a disulfide-linked homodimer protein, with each Fn polypeptide consisting of three types of repeating modules: 12 type I, 2 type II, and 15-17 type III modules. To determine the epitope on Fn recognized by C. perfringens cells, anti-Fn monoclonal antibodies (mAbs) and various Fn fragments (III2-10, rIII2-4, rIII5-7, rIII8, rIII9, rIII10) were employed. Although two C. perfringens-derived Fn-binding proteins, FbpA and FbpB, have been reported, they appear not to be the bacterium's surface Fn receptor. Moreover, both FbpA and FbpB were found to bind to C. perfringens cells. To avoid confusion, a mutant C. perfringens lacking both the fbpA and fbpB genes (MW5) was prepared using an in-frame deletion system. MW5 cells bound Fn on their surface, suggesting the presence of a putative Fn receptor(s) on C. perfringens cells. Of several anti-Fn mAbs, both HB39 and MO inhibited the binding of Fn to MW5 cells. HB39 reacted strongly with III2-10 and rIII9, and weakly with rIII2-4, rIII10 and rIII5-7 in Western blotting analysis. Binding of HB39 to Fn was inhibited in the presence of either rIII9 or rIII10, but not in the presence of rIII2-4, rIII5-7, or rIII8. Binding of Fn to MW5 cells was strongly inhibited by both III2-10 and rIII9, marginally inhibited by rIII2-4, but not affected by rIII5-7, rIII8, or rIII10. Significant binding of MW5 cells to immobilized rIII9 and rIII10 as well as immobilized III2-10 was observed. The region of Fn recognized by C. perfringens was thus mapped to the region encompassed by III9 and III10.

Adhesive properties of Clostridium perfringens to extracellular matrix proteins collagens and fibronectin.

The adhesive properties of Clostridium perfringens to collagens, gelatin, fibronectin (Fn), Fn-prebound collagens, and Fn-prebound gelatin were investigated. C. perfringens could bind to Fn-prebound collagen type II, type III, and gelatin, but not to gelatin or collagens except for collagen type I directly. Recombinant Fn-binding proteins of C. perfringens, rFbpA and rFbpB, were used to examine Fn-mediated bacterial adherence to collagen type I. In the presence of rFbps, C. perfringens adherence to Fn-prebound collagen type I was inhibited in a dose-dependent manner. Fn was not released from the coated collagen type I by the presence of rFbps, and rFbps did not bind to collagen type I. Thus, the inhibition of C. perfringens binding to Fn-prebound collagen type I by rFbps could not be explained by the removal of Fn from collagen or by the competitive binding of rFbps to collagen. Instead, both rFbps were found to bind to C. perfringens. These results suggest the possibility that rFbps may bind to the putative Fn receptor expressed on C. perfringens and competitively inhibit Fn binding to C. perfringens.

Frequency of emerging positive diffusion-weighted imaging in early repeat examinations at least 24 h after transient ischemic attacks.

INTRODUCTION: The relationships between diffusion lesions and risk scores for patients with a Transient ischemic attack (TIA) and the optimal timing for diffusion lesion screening have not been characterized. The purpose of our study was to evaluate the appearance of diffusion-weighted imaging (DWI) lesions during follow-up examinations of patients with TIA or minor stroke without initial DWI lesions. METHODS: We identified 31 patients who did not show diffusion lesions in initial DWI. A second magnetic resonance imaging (MRI) examination was performed 24 h after the initial MRI, and the patients were divided into two groups based on the results. Demographic and clinical data, including initial National Institutes of Health Stroke Scale scores, ABCD and ABCD(2) scores, and other MRI findings were evaluated. The data were analyzed using Spearman's rank tests and unpaired t tests. RESULTS: Ten patients (32.3 %) showed diffusion lesions on the second DWI examination. Both risk scores were higher in these patients compared with patients with negative results on follow-up DWI (P < 0.05, unpaired t test) and correlated with the length of the TIA (R s = 0.017, P < 0.05; R s = 0.003, P < 0.01; Spearman's rank test). CONCLUSION: Our results suggest that TIA patients with high-risk scores might be underestimated if the first MRI was performed within 24 h of symptom onset.

Dynamic susceptibility contrast perfusion weighted imaging in grading of nonenhancing astrocytomas.

PURPOSE: To evaluate if the relative tumor blood volume (rTBV) using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) can aid in distinguishing low- from high-grade nonenhancing astrocytomas. MATERIALS AND METHODS: Seventeen patients with histologically proven astrocytomas underwent MRI including DSC-MRI. Maximum TBV regions of interest were recorded from each neoplasm and normalized to contralateral normal white matter. Demographic features, diagnostic MRI findings including tumor volumes, and the normalized rTBV ratios were compared between low-grade (I and II, LGA, n = 6) and high-grade (III) astrocytomas (HGA, n = 11) using Mann-Whitney's U-test and receiver operating characteristic (ROC) analysis. RESULTS: Maximum rTBV ratios were statistically higher for HGA (1.11 ± 0.13) than LGA (0.66 ± 0.17, P < 0.005) with the best cutoff threshold at 0.94 (sensitivity of 90.9%, specificity of 100%). Differences in mean age and tumor volume on fluid-attenuated inversion recovery (FLAIR) imaging between the two groups did not reach statistical difference (P = 0.22, 0.36). CONCLUSION: The addition of DSC-MRI can aid in accurate grading of nonenhancing astrocytomas with high sensitivity and specificity.

Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T(2)*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator.

BACKGROUND: The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. METHODS: We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. RESULTS: The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. CONCLUSIONS: Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.

Impact of complete recanalization on clinical recovery in cardioembolic stroke patients with M2 occlusion.

BACKGROUND AND PURPOSE: We investigated the impact of complete recanalization beyond partial recanalization in distal (M2) middle cerebral artery (MCA) occlusion. METHODS: Data regarding M2 occlusion patients treated with endovascular thrombectomy (EVT) and/or intravenous thrombolysis (tPA) were reviewed from our prospective EVT registry and multicenter tPA (YAMATO study) data bank. Complete recanalization was modified thrombolysis with cerebral infarction score (TICI) of 3 at the end of EVT or similar appearances of both MCAs on magnetic resonance angiography (MRA) within 1.5 h after tPA. Partial recanalization was defined as TICI ≥2b or > 50% recanalization on MRA. At 3 months, favorable outcome was defined as a modified Rankin Scale score ≤ 2. RESULT: Data on 121 patients were analyzed. EVT-alone was in 38 patients; combined EVT and tPA in 28; and tPA-alone in 55. Complete recanalization was achieved in 27 (22%), partial recanalization in 48 (40%), and no-to-limited recanalization in 46 (38%). At 3 months, 51% of patients had favorable outcomes, and this rate was significantly higher in the complete recanalization group than in the partial and no-to-limited recanalization groups (75% vs. 41% vs. 49%, p = .043). Multivariate regression analysis showed that complete recanalization was an independent parameter related to favorable outcomes (odds ratio 4.78, 95% CI: 1.16-19.73, p = .030). However, combined complete and partial recanalization was not associated with favorable outcomes (odds ratio 1.49, 95% CI 0.53-4.22, p = .449). CONCLUSION: Complete recanalization, but not partial recanalization, at the end of EVT and tPA therapy is associated with favorable outcomes in patients with M2 occlusion.

5,5-Dimethyl-3-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-1-phenyl-3-(trifluoromethyl)-3,5,6,7-tetrahydro-1H-indole-2,4-dione, a potent inhibitor for mammalian elongase of long-chain fatty acids family 6: examination of its potential utility as a pharmacological tool.

Long-chain fatty acid elongases reside in the endoplasmic reticulum and are responsible for the rate-limiting step of the elongation of long-chain fatty acids. The elongase of long-chain fatty acids (ELOVL) family 6 (ELOVL6) is involved in the elongation of saturated and monosaturated fatty acids. Increased expression of ELOVL6 in ob/ob mice suggests a role for ELOVL6 in metabolic disorders. Furthermore, ELOVL6-deficient mice are protected from high-fat diet-induced insulin resistance, which suggests that ELOVL6 might be a new therapeutic target for diabetes. As reported previously, we developed a high-throughput screening system for fatty acid elongases and discovered lead chemicals that possess inhibitory activities against ELOVL6. In the present study, we examined in detail the biochemical and pharmacological properties of 5,5-dimethyl-3-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-1-phenyl-3-(trifluoromethyl)-3,5,6,7-tetrahydro-1H-indole-2,4-dione (Compound-A), a potent inhibitor of ELOVL6. In in vitro assays, Compound-A dose-dependently inhibited mouse and human ELOVL6 and displayed more than 30-fold greater selectivity for ELOVL6 over the other ELOVL family members. In addition, Compound-A effectively reduced the elongation index of fatty acids of hepatocytes, suggesting that Compound-A penetrates the cell wall and inhibits ELOVL6. More importantly, upon oral administration to mice, Compound-A showed high plasma and liver exposure and potently reduced the elongation index of the fatty acids of the liver. This is the first study to report a potent and selective inhibitor of mammalian elongases. Furthermore, Compound-A seems to be a useful tool to further understand the physiological roles of ELOVL6 and to evaluate the therapeutic potential of an ELOVL6 inhibitor.

Evaluation of initial diffusion-weighted image findings in acute stroke patients using a semiquantitative score.

PURPOSE: We evaluated the usefulness of rating diffusion-weighted images (DWI) using a semiquantitative score modified from the Alberta Stroke Programme Early CT Score (ASPECTS) to predict deterioration of neurological symptoms in patients with hyperacute ischemic stroke who had undergone thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). MATERIALS AND METHODS: We examined 22 patients with acute stroke (14 men, 8 women, mean age 72.5 years) treated with intravenous rt-PA. All were assessed using the National Institutes of Health Stroke Scale (NIHSS) and underwent emergent magnetic resonance (MR) imaging within 3 hours and 24 hours of stroke onset. Patients were divided into a deteriorated group (16 patients), in which NIHSS scores were increased after thrombolysis, and a non-deteriorated group (6 patients). We compared the DWI score, ASPECTS, and volume of hyperintense ischemic lesion on DWI (DWI volume) of the 2 groups and examined correlations between these scores and initial NIHSS score or DWI volume. RESULTS: The DWI score and ASPECTS tended to be lower in the deteriorated group than the non-deteriorated group. In addition, with a cutoff value

[Comparison with bone scintigraphy and MDCT findings in patients with round focal accumulation on bone scintigraphy].

PURPOSE: This study aimed to compare with bone scintigraphy showed round focal accumulation and Multidetector Row CT (MDCT) findings. METHODS: We obtained 101 patients (mean age 69.2 years; 75 men, 26 women) and 186 diseases. They were examined both MDCT and bone scintigraphy within a month of each other. We classified into two groups (with metastasis and spondylosis) according to their MDCT findings. Bone scintigraphy was estimated on planar image, MDCT was evaluated in three directions with 1 x 1 x 1 mm thickness. RESULTS: We determined 20 metastases cases and 81 of spondylosis. We could not judge abnormal findings on MDCT in 4 patients (1 metastasis, 3 spondylosis); thus, detectability by MDCT was 93.5%. In the spondylosis group, the accumulation lesions were localized on the lower vertebral body in 76 patients (59%), with most showing as osteophytes. In the metastasis group, 11 patients showed more than 1 accumulations, 9 were osteoblastic changes and 10 were lytic. There was a tendency that patients who accumulated more than 1 vertebral bodies (64%) had osteoblastic and irregular distribution and those who accumulated just one body (78%) were lytic and their locations were focused on the lateral side. CONCLUSION: For evaluating bone scintigraphy, MDCT finding was helpful to increase the detectability in bone metastasis. Therefore, we should refer to MDCT finding positively in reading bone scintigraphy.

Diabetes mellitus inhibits complete recanalization in patients with middle cerebral artery occlusion.

Methods: This was a retrospective cohort study. Data from 165 patients, with middle cerebral occlusion before t-PA therapy (from the YAMATO study databank), were retrospectively evaluated. Patients were classified into diabetic (D) or non-diabetic (ND) groups based on the history of diabetes mellitus (DM) or hemoglobin A1c levels of ≥ 6.5%. Arterial recanalization was assessed using magnetic resonance angiography or digital subtraction angiography at 2 points: 1) early recanalization, within 2 h; 2) delayed complete recanalization at 24 h. Good clinical outcome was defined as modified Rankin Scale score 0-2 at 3 months. Results: A total of 33 (21%) were classified into the D and 127 (79%) in the ND groups. Early recanalization was similarly in the D and ND groups (61% vs. 52%, p = 0.434). However, complete recanalization at 24 h was infrequent in the D group (13% vs. 43%, p = 0.002). Among patients with early recanalization, 4 (22%) of 18 patients in the D group and 32 (56%) of 57 patients in the ND group had complete recanalization at 24 h (p = 0.015); while among those without early recanalization, 17 (30%) in the ND and none in the D groups had complete recanalization at 24 h (p = 0.028). Multivariate regression analysis showed DM was one of the independent negative factors for complete recanalization at 24 h (odds ratio 0.113, 95%CI: 0.027-0.472, p = 0.003). At 3 months, group with complete recanalization at 24 h achieved higher frequency of good outcome (67% vs. 49%, p = 0.046). Conclusion: Diabetes might be a risk factor of incomplete recanalization at 24 h regardless of early recanalization.

Comparison of monophasic versus biphasic stimulation in rTMS over premotor cortex: SEP and SPECT studies.

OBJECTIVE: To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. METHODS: In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. RESULTS: Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. CONCLUSIONS: Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. SIGNIFICANCE: Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.

Ischemic findings of T2*-weighted 3-tesla MRI in acute stroke patients.

BACKGROUND: We compared ischemic findings on gradient echo-type T(2)*-weighted images at 3-tesla MRI (T(2)*WI) in patients with acute ischemia and major vessel occlusion, and stroke patients with lacunar infarction or branch atheromatous disease. METHODS: Our study population consisted of 45 patients with acute stroke. They underwent 3-tesla MRI within 12 h of stroke onset. Included were 24 patients (13 men and 11 women, mean age 68 years) with major vessel occlusion and 21 patients (11 men and 10 women, mean age 69 years) with minor infarction such as lacunar infarcts or branch atheromatous disease. We classified vascular ischemic findings of T(2)*WI into 3 sign categories, i.e. artery susceptibility sign, cortical vessel sign (hypointensity and enlargement of the cortical vessels) and brush sign (hypointensity of vessels in the deep white matter). Decreased intensity in the ischemic parenchyma was designated ischemic tissue sign. We compared regions of interest in the hypoperfused area on flow-sensitive alternating inversion recovery (FAIR) images with our vascular ischemic findings. RESULTS: None of the vascular ischemic signs nor the ischemic tissue sign were found in patients with minor vessel disease. All 24 patients with major vessel occlusion manifested the cortical vessel sign, 23 the brush sign. The area with ischemic vessel signs on T(2)*WI was almost as large or somewhat smaller than the hypoperfused area on FAIR images. Compared to the contralateral side, 14 of 24 patients (58.3%) with major vessel occlusion showed decreased intensity in the ischemic parenchyma (ischemic tissue sign). Region of interest measurements on FAIR images demonstrated greater hypoperfusion in the area classified as ischemic tissue sign on T(2)*WI. CONCLUSIONS: Ischemic vessel signs and the ischemic tissue sign on T(2)*WI at 3 T would be useful to evaluate the extensive ischemia due to major vessel occlusion and may be correlated with the blood-oxygen-level-dependent effect due to increased deoxyhemoglobin. The ischemic tissue sign may be reflective of severe ischemia.

Does partial volume corrected maximum SUV based on count recovery coefficient in 3D-PET/CT correlate with clinical aggressiveness of non-Hodgkin's lymphoma?

OBJECTIVE: There is much controversy about the correlation between the degree of 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) uptake and clinical aggressiveness of non-Hodgkin's lymphoma (NHL). In this study, we investigated whether partial volume corrected FDG uptake based on count recovery coefficient in 3D-positron emission tomography (PET)/computed tomography (CT) correlates with the clinical aggressiveness of NHL and improves diagnostic accuracy. METHODS: Forty-two patients with NHL underwent FDG-PET/CT scans (26 aggressive NHLs and 16 indolent ones). Count recovery curve was obtained using NEMA 2001 body phantom. Scan protocol and reconstructive parameters in the phantom study were the same as those in a clinical scan except for emission time. Relative recovery coefficient (RC) was calculated as RC = A/B (A, maximum pixel count of each hot sphere; B, maximum pixel count of greatest sphere). Partial volume corrected maximum count of standardized uptake value (PVC-SUV) was calculated as PVC-SUV = NC-SUV/RC (NC-SUV: non-corrected maximum count of SUV). Three parameters (NC-SUV, PVC-SUV, and size) between aggressive and indolent NHLs were compared. RESULTS: Significant differences were shown in all parameters between aggressive and indolent NHLs. Means +/- SD of NC-SUV, PVC-SUV, and size was as following: NC-SUV (15.3 +/- 6.9, 8.7 +/- 7.0; P < 0.01), PVC-SUV (18.2 +/- 8.1, 12.7 +/- 7.8; P < 0.05), and size (mm, 32.4 +/- 18.3, 21.9 +/- 10.3; P < 0.05). When an NC-SUV of 9.5 was the cutoff for aggressive NHL, the receiver-operating-characteristic (ROC) analysis correctly identified 21 of 26 aggressive ones. Sensitivity and specificity were 81% each, and the positive and negative predictive values were 88% and 72%, respectively. When a PVCSUV of 11.2 was the cutoff, the ROC analysis revealed 81% sensitivity, 63% specificity, and positive and negative predictive values of 78% and 67%, respectively. At a cutoff for aggressive NHL of a size of 27 mm, the ROC analysis revealed 50% sensitivity, 81% specificity, and positive and negative predictive values of 81% and 50%, respectively. The comparison of area under the curve in ROC analyses indicated that NC-SUV showed the greatest diagnostic accuracy (NC-SUV 0.84, PVC-SUV 0.72, and size 0.69). CONCLUSIONS: Diagnostic accuracy of PVC-SUV was inferior to that of NC-SUV. These results suggest that NC-SUV, which contains information on both size and FDG density, provides better differentiation between aggressive and indolent NHLs than PVC-SUV.

FDG-PET/CT for cancer management.

FDG-PET/CT is increasingly being used for staging, restaging, and treatment monitoring for cancer patients. The introduction of a PET/CT system enables both morphological and metabolic imaging to be performed in a single session. Knowledge of the normal physiologic distribution of FDG and an understanding of the clinical indications and limitations of PET/CT enable accurate diagnosis and thus a better level of care for patients.