Comparison of CBF between pCASL and SPECT

Purpose: We compared the regional cerebral blood flow (rCBF) obtained by pulsed continuous arterial spin labeling (pCASL) and iodine-123-N-isopropyl-p-iodoamphetamine (IMP) single photon emission computed tomography (SPECT) using 3-dimensional stereotactic region-of-interest (ROI) software for automated definition of ROIs in anatomic regions of the brain. Methods: Thirteen patients with cerebrovascular occlusive disease and three with transient ischemic attacks underwent pCASL and IMP SPECT imaging. We compared rCBF values of each anatomic region and calculated the correlation coefficients between pCASL and IMP SPECT. We also calculated the asymmetry index (AI) using ROIs in contralateral regions of the hemispheres. Results: The rCBF values calculated from pCASL and IMP SPECT were comparable in most segments, but rCBF in the thalamus (P < 0.0001) and hippocampus (P = 0.0006) was significantly higher measured by pCASL than IMP SPECT. The correlation of rCBF between pCASL and IMP SPECT in the affected hemisphere (r = 0.50) tended to be lower than that in the normal hemisphere (r = 0.59), but not significantly different (P = 0.25). Moreover, there was a fixed bias for underestimation of rCBF by pCASL (P = 0.0047) in the affected hemisphere. The calculated AI showed a significant relationship between methods (r = 0.79, P < 0.0001). Conclusion: The rCBF obtained by pCASL had positive relationships with IMP SPECT. However, it should be considered that pCASL tends to have a weak relationship with IMP SPECT in some normal regions and regions affected by cerebrovascular occlusive disease

Alteration of default mode network in children with autism spectrum disorder

Purpose : The purpose of this study was to investigate changes in the functional connectivity of the default mode network (DMN) in normal aging and in children with autistic spectrum disorder (ASD) by using resting-state functional magnetic resonance imaging (rsfMRI) and independent component analysis. Methods : Thirty-one healthy controls (HC) in four age groups (1-3, 4-8, 20-29, and 50-59 years) and 14 childhood ASD cases (1-8 years of age) were examined by rsfMRI echo-planar imaging on a clinical 3-T MRI scanner. Imaging of all children (1-8 years) was conducted under sedation, while adults were scanned in the awake state with eyes closed. Results : The regions of DMN functional connectivity in the bilateral inferior parietal lobule and posterior cingulate cortex were smaller in HC children than in HC adults, and smaller in the ASD group than in the HC children. Conclusion : It is possible to observe developmental and pathological changes in the DMN by rsfMRI. Reduced DMN functional connectivity in children may be a useful biomarker for ASD diagnosis

双極性障害におけるグルタミン酸神経伝達異常に関するMRS研究

Background: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system. Methods: Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence. Results: After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG. Limitations: The present findings are cross-sectional and metabolites were measured in only two regions. Conclusions: Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD

Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Variable indoleamine 2,3‐dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2, 3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings