Effect of Long-Term Hypoxia on Myocardial Alpha1- Receptors

To determine the developmental changes in myocardial α1-adrenergic receptor system, we employed [3H-Prazosin] binding technique to characterize α1-adrenergic receptors in both fetal and adult sheep myocardial ventricular membrane preparations. Myocardial α1-adrenergic receptor density (Bmax) declined during developmental process with both fetal left ventricle(LV) and fetal right ventricle(RV) having significantly more binding sites than respective adult ventricles. We also demonstrated that the positive inotropic response to the α1-adrenergic agonist phenylephrine did not differ significantly between the fetal and adult ventricles. The present study also investigated the effect of long-term high-altitude hypoxemia on the α1- and β1-adrenergic receptor interaction in the heart. The interactions between two receptor systems were examined by prior stimulation of muscles with α1-adrenergic agonist phenylephrine (PHE). Hypoxic left ventricle without prior phenylephrine stimulation produced greater response to isoproterenol stimulation {maximal tension developed (Tmax, g/mm2 =: 1.16 ± 0.18)}; than normoxic left ventricle without prior phenylephrine stimulation {maximal tension developed (Tmax, g/mm2 =: 0.41 ± 0.05)} (p\u3c0.01). Mycocardial α1- and β1-adrenergic antagonistic interaction was observed only in hypoxic LV. In conclusion, chronic hypoxemia augmented isoproterenol dose-responses in hypoxic left ventricle. Phenylephrine antagonized effects of isoproterenol in hypoxic left ventricle indicating an α1- and β1-adrenergic interaction during long-term high-altitude hypoxemia. To determine the effects of long-term high-altitude hypoxemia on myocardial α1-adrenergic receptor system and Ins(1,4,5)P3 (IP3) responses, we employed [3H-Prazosin] binding technique and Ins(1,4,5)P3 assay to characterize α1-adrenergic receptors and Ins( 1,4,5)P3 in the sheep myocardial preparations. Long-term high-altitude hypoxemia significantly depressed myocardial α1-adrenergic receptor density (Bmax in fmol/mg) in fetal right ventricle (RV). In contrast, it did not affect the dissociation constant (Kd). Long-term hypoxemia also significantly decreased Ins(1,4,5)P3 production in response to phenylephrine stimulation in the fetal right ventricle. In conclusion, myocardial α1-adrenergic receptor density and Ins(1,4,5)P3 production in response to agonist stimulation in the fetal right ventricle were decreased as result of long-term high-altitude hypoxemia

Evaluation of skeletal muscle perfusion in a canine hind limb ischemia model using CT perfusion imaging

PURPOSE:To evaluate skeletal muscle perfusion in a canine hind limb ischemia model using CT perfusion imaging (CTPI).METHODS:Twelve beagles underwent embolization at the branch of the left deep femoral artery. The right hind limbs were used as controls. CTPI was performed immediately after embolization. The perfusion parameters of the regions of interest (ROI), including blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability (PMB), were obtained in both the lateral and posterior hind limb muscle groups.RESULTS:After embolization, the BV, BF and PMB values in the lateral muscles of the left hind limbs were significantly lower than those in the right hind limbs (P > 0.05), and the MTT was significantly prolonged (P > 0.05). The values for BV, BF, MTT and PMB in the posterior muscles of the left hind limbs were not significantly different from those in the right hind limbs (P > 0.05). The values for BV, BF and PMB in the lateral muscles of the left hind limbs were significantly lower than those in the posterior muscles of the left hind limbs (P > 0.05).CONCLUSION:CTPI could be used to evaluate skeletal muscle perfusion in a canine model, which may have clinical relevance in lower limb ischemia and vascular reconstruction

Differentiating Peripherally-Located Small Cell Lung Cancer From Non-small Cell Lung Cancer Using a CT Radiomic Approach

Lung cancer can be classified into two main categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which are different in treatment strategy and survival probability. The lung CT images of SCLC and NSCLC are similar such that their subtle differences are hardly visually discernible by the human eye through conventional imaging evaluation. We hypothesize that SCLC/NSCLC differentiation could be achieved via computerized image feature analysis and classification in feature space, as termed a radiomic model. The purpose of this study was to use CT radiomics to differentiate SCLC from NSCLC adenocarcinoma. Patients with primary lung cancer, either SCLC or NSCLC adenocarcinoma, were retrospectively identified. The post-diagnosis pre-treatment lung CT images were used to segment the lung cancers. Radiomic features were extracted from histogram-based statistics, textural analysis of tumor images and their wavelet transforms. A minimal-redundancy-maximal-relevance method was used for feature selection. The predictive model was constructed with a multilayer artificial neural network. The performance of the SCLC/NSCLC adenocarcinoma classifier was evaluated by the area under the receiver operating characteristic curve (AUC). Our study cohort consisted of 69 primary lung cancer patients with SCLC (n = 35; age mean ± SD = 66.91± 9.75 years), and NSCLC adenocarcinoma (n = 34; age mean ± SD = 58.55 ± 11.94 years). The SCLC group had more male patients and smokers than the NSCLC group (P \u3c 0.05). Our SCLC/NSCLC classifier achieved an overall performance of AUC of 0.93 (95% confidence interval = [0.85, 0.97]), sensitivity = 0.85, and specificity = 0.85). Adding clinical data such as smoking history could improve the performance slightly. The top ranking radiomic features were mostly textural features. Our results showed that CT radiomics could quantitatively represent tumor heterogeneity and therefore could be used to differentiate primary lung cancer subtypes with satisfying results. CT image processing with the wavelet transformation technique enhanced the radiomic features for SCLC/NSCLC classification. Our pilot study should motivate further investigation of radiomics as a non-invasive approach for early diagnosis and treatment of lung cancer

Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm

IntroductionStudies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown.MethodsTo examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions.ResultsCompared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = −0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350).DiscussionThe decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA

Gray matter density reduction associated with adjuvant chemotherapy in older women with breast cancer

PURPOSE: The purpose of this study was to evaluate longitudinal changes in brain gray matter density (GMD) before and after adjuvant chemotherapy in older women with breast cancer. METHODS: We recruited 16 women aged ≥ 60 years with stage I-III breast cancers receiving adjuvant chemotherapy (CT) and 15 age- and sex-matched healthy controls (HC). The CT group underwent brain MRI and the NIH Toolbox for Cognition testing prior to adjuvant chemotherapy (time point 1, TP1) and within 1 month after chemotherapy (time point 2, TP2). The HC group underwent the same assessments at matched intervals. GMD was evaluated with the voxel-based morphometry. RESULTS: The mean age was 67 years in the CT group and 68.5 years in the HC group. There was significant GMD reduction within the chemotherapy group from TP1 to TP2. Compared to the HC group, the CT group displayed statistically significantly greater GMD reductions from TP1 to TP2 in the brain regions involving the left anterior cingulate gyrus, right insula, and left middle temporal gyrus (pFWE(family-wise error)-corrected < 0.05). The baseline GMD in left insula was positively correlated with the baseline list-sorting working memory score in the HC group (pFWE-corrected < 0.05). No correlation was observed for the changes in GMD with the changes in cognitive testing scores from TP1 to TP2 (pFWE-corrected < 0.05). CONCLUSIONS: Our findings indicate that GMD reductions were associated with adjuvant chemotherapy in older women with breast cancer. Future studies are needed to understand the clinical significance of the neuroimaging findings. This study is registered on ClinicalTrials.gov (NCT01992432)

Cortical Surface Area Rather Than Cortical Thickness Potentially Differentiates Radiation Encephalopathy at Early Stage in Patients With Nasopharyngeal Carcinoma

Radiation encephalopathy (RE) is one of the most severe complications in nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). However, the morphological alteration of early RE is insufficiently investigated. We aimed to investigate the cortical thickness and surface area alterations in NPC patients with or without RE in the follow-up. A total of 168 NPC patients each underwent a single scan and analysis at various times either Pre-RT (n = 56) or Post-RT (n = 112). We further divided the Post-RT NPC patients into three groups based on the time of the analysis following RT (Post-RTwithin 6 months and Post-RT7-12 months) or whether RE signs were detected in the analysis (Post-RTRE proved in follow-up). We confined the vertex-wise analyses of the cortical thickness and surface area to the bilateral temporal lobes. Interestingly, we revealed a gradual increase in the cortical surface area of the temporal lobe with increasing time after RT within the Post-RTRE proved in follow-up group, consistent with the between-group findings, which showed a significant increase in cortical surface area in the Post-RTRE proved in follow-up group relative to the Pre-RT group and the Post-RTwithin 6 months group. By contrast, such a trend was not observed in the cortical thickness findings. We concluded that the cortical surface area, rather than cortical thickness, may serve as a potential biomarker for early diagnosis of RE

Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: a pilot longitudinal study

Purpose Older cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer. Methods Chemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60–82 years) with stage I-III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo), were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed. Results In the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected=0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected=0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance. Conclusions Our study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer

Effects of chemotherapy on aging white matter microstructure: a longitudinal diffusion tensor imaging study

Objective: We aimed to use diffusion tensor imaging (DTI) to detect alterations in white matter microstructure in older patients with breast cancer receiving chemotherapy. Methods: We recruited women age ≥60 years with stage I-III breast cancer (chemotherapy [CT] group; n = 19) to undergo two study assessments: at baseline and within one month after chemotherapy. Each assessment consisted of a brain magnetic resonance imaging scan with DTI and neuropsychological (NP) testing using the National Institutes of Health (NIH) Toolbox Cognition Battery. An age- and sex-matched group of healthy controls (HC, n = 14) underwent the same assessments at matched intervals. Four DTI parameters (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) were calculated and correlated with NP testing scores. Results: For CT group but not HCs, we detected statistically significant increases in MD and RD in the genu of the corpus callosum from time point 1 to time point 2 at p 0.05). Conclusions: We identified alterations in white matter microstructures in older women with breast cancer undergoing chemotherapy. These findings may potentially serve as neuroimaging biomarkers for identifying cognitive impairment in older adults with cancer

Neuroimaging features of primary central nervous system post-transplantation lymphoproliferative disorder following hematopoietic stem cell transplant in patients with β-thalassemia: a case series and review of literature

Abstract Purpose Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT) in patients with severe β-thalassemia. This study aimed to assess the clinical presentation, pathological characteristics, neuroimaging findings, and treatment strategies in patients with β-thalassemia who developed PCNS-PTLD and to compare a case series from our transplant center to reported cases from literature. Methods We retrospectively reviewed our hospital database and identified four cases of pathologically confirmed PCNS-PTLD without a history of systemic PTLD in patients with severe β-thalassemia after HSCT. We also performed a relevant literature review on PCNS-PTLD. Results The median time from transplantation to diagnosis of PCNS-PTLD was 5.5 months. Intracerebral lesions were usually multiple involving both supratentorial and infratentorial regions with homogeneous or rim enhancement. All patients had pathologically confirmed PCNS-PTLD with three patients having diffuse large B-cell lymphoma and the fourth patient having plasmacytic hyperplasia. There was low response to treatment with a median survival of 83 days. Conclusion PCNS-PTLD should be considered in the differential diagnosis of patients with β-thalassemia who had an intracranial lesion on neuroimaging after HSCT. Critical relevance statement This case series with a comprehensive review of neuroimaging and clinical characteristics of children with primary central nervous system post-transplantation lymphoproliferative disorder should advance our understanding and improve management of this rare yet severe complication following transplant for β-thalassemia. Key points • We assessed clinical presentation, treatment strategies, and neuroimaging characteristics of PCNS-PTLD in patients with β-thalassemia after transplantation. • Patients with β-thalassemia may have post-transplantation lymphoproliferative disorder presenting as brain lesions on neuroimaging. • Neuroimaging findings of the brain lesions are helpful for prompt diagnosis and proper management. Graphical Abstrac

Brain Imaging and Overall Survival after Allogeneic Hematopoietic Cell Transplantation

Aim: We conducted a retrospective review of all brain imaging studies in the first year after allogeneic haematopoietic cell transplantation (HCT) to determine (a) the percentage of patients with CNS neurological complications based solely on undergoing brain imaging, (b) transplant-related risk factors of undergoing brain imaging, and (c) overall survival in the patients with neurological complications compared to those transplant patients who did not have brain imaging. Methods: Subjects were 543 consecutive recipients (August 2004-August 2007) of allogeneic HCT followed for overall survival for up to 6 years after HCT. Comparisons between patient groups with brain imaging and without brain imaging were tested using the Pearson chi-square test. Survival analyses with outcome time-to-brain-scan started at date of transplant and used Kaplan-Meier methods. Results: Of 543 HCT recipients, 128 patients (24%) underwent brain imaging during the first year after transplantation. There was a greater risk of brain imaging in unrelated donor transplants and in lymphoid as opposed to myeloid malignancies (respective hazard ratios 1.45 and 1.43, P=0.04). Overall survival was significantly worse in unrelated donor transplants (hazard ratio 1.42, P=0.003) and in cord blood transplants (hazard ratio 1.68, P=0.02). Landmark survival analysis of patients alive 1 year after HCT showed worse survival over the next 5 years in those who had brain imaging in the first post transplant year (P<0.0001). Conclusion: These results suggest that development of neurological symptoms or a sign sufficient to prompt clinicians to order brain imaging early after HCT identifies a poor prognosis in transplant population