Semi-quantitative Analysis Technique Research Articles

Patterns of Tau pathology in patients with anti-IgLON5 disease visualized by Florzolotau (18F) PET.

Anti-IgLON5 disease is a rare autoimmune neurological disorder with prominent Tau protein deposits in the brainstem and hypothalamus. The aim of this study was to visualize the in vivo distribution patterns of Tau protein in patients with anti-IgLON5 disease using the second-generation Tau PET tracer, Florzolotau (18F) PET imaging. Patients diagnosed with anti-IgLON5 disease were enrolled consecutively. Age- and sex-matched healthy controls (HCs) were also enrolled. The uptake of Florzolotau (18F) and 18F-FDG was assessed using both visual and semi-quantitative analysis techniques. A total of 10 patients with anti-IgLON5 disease and 40 HCs were included in the study. All ten patients with anti-IgLON5 disease underwent Florzolotau (18F) PET scans, and five of them underwent 18F-FDG PET scans. Twenty HCs underwent Florzolotau (18F) PET scans, and the remaining 20 HCs underwent 18F-FDG PET scans. In patients with anti-IgLON5 disease, significant uptake of Florzolotau (18F) was observed predominantly in the midbrain, pons, cerebellum, caudate, and putamen. This uptake pattern was notably absent in the control group. Moreover, semi-quantitative analysis techniques demonstrated widespread hypometabolism in the cerebral cortex in patients with anti-IgLON5 disease. This study indicates distinct Tau protein deposition patterns in patients with anti-IgLON5 disease, potentially serving as imaging biomarkers.

Automated semi-quantitative amyloid PET analysis technique without MR images for Alzheimer’s disease

ObjectiveAlthough beta-amyloid (Aβ) positron emission tomography (PET) images are interpreted visually as positive or negative, approximately 10% are judged as equivocal in Alzheimer’s disease. Therefore, we aimed to develop an automated semi-quantitative analysis technique using 18F-flutemetamol PET images without anatomical images.MethodsOverall, 136 cases of patients administered 18F-flutemetamol were enrolled. Of 136 cases, five PET images each with the highest and lowest values of standardized uptake value ratio (SUVr) of cerebral cortex-to-pons were used to create positive and negative templates. Using these templates, PET images of the remaining 126 cases were standardized, and SUVr images were produced with the pons as a reference region. The mean of SUVr values in the volume of interest delineated on the cerebral cortex was compared to those in the CortexID Suite (GE Healthcare). Furthermore, centiloid (CL) values were calculated for the 126 cases using data from the Centiloid Project (http://www.gaain.org/centiloid-project) and both templates. 18F-flutemetamol-PET was interpreted visually as positive/negative based on Aβ deposition in the cortex. However, the criterion "equivocal" was added for cases with focal or mild Aβ accumulation that were difficult to categorize. Optimal cutoff values of SUVr and CL maximizing sensitivity and specificity for Aβ detection were determined by receiver operating characteristic (ROC) analysis using the visual evaluation as a standard of truth.ResultsSUVr calculated by our method and CortexID were highly correlated (R2 = 0.9657). The 126 PET images comprised 84 negative and 42 positive cases of Aβ deposition by visual evaluation, of which 11 and 10 were classified as equivocal, respectively. ROC analyses determined the optimal cutoff values, sensitivity, and specificity for SUVr as 0.544, 89.3%, and 92.9%, respectively, and for CL as 12.400, 94.0%, and 92.9%, respectively. Both semi-quantitative analyses showed that 12 and 9 of the 21 equivocal cases were negative and positive, respectively, under the optimal cutoff values.ConclusionsThis semi-quantitative analysis technique using 18F-flutemetamol-PET calculated SUVr and CL automatically without anatomical images. Moreover, it objectively and homogeneously interpreted positive or negative Aβ burden in the brain as a supplemental tool for the visual reading of equivocal cases in routine clinical practice.

Clinical relevance of early sublingual microcirculation monitoring in septic shock patients.

Although microcirculation dysfunction plays unique role in septic shock, translation of microcirculation to clinical practices is limited by current semi-quantities analysis and unclear clinical relevance of microcirculation monitoring. Our aim was to critically evaluate the characteristic nature and relevant clinical important of microcirculation. Pubmed (2000 to August 2015) were searched to identify observation, case-control, intervention and randomized clinical studies evaluating the relationship between microcirculation alterations and mortality, morbidity and drug responses. The STROBE and CONSORT Statement for assessment of the quality of included studies. We examined results from 17 observations, 4 randomized controlled trials and one case report published studies. This data set comprised of 637 patients. Early septic shock is associated with hypoperfusion and heterogeneous microcirculation that is associated with hyperlactemia and metabolic acidosis. The evidence on clinical relevance of microcirculation is less striking, mainly due to the limited number of studies and problems related to the methodological protocol of the studies and currently semi-quantitative analysis technique. In particular the baseline and time course of microcirculation alteration appears to be controversial. There is lack of evidences of clinical importance of early microcirculation monitoring and mechanism of microcirculation dysfunction in septic shock patients. This could be due to the methodological protocol of the studies and currently semi-quantitative analysis technique.

Albumin microvascular leakage in brains with diabetes mellitus.

Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood-brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi-quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833-837, 2016. © 2016 Wiley Periodicals, Inc.

Micro-computed tomography–based highly automated 3D segmentation of the rat spine for quantitative analysis of metastatic disease

Noninvasive evaluation of metastatic disease in the spine has generally been limited to 2D qualitative or semiquantitative analysis techniques. This study aims to develop and evaluate a highly automated micro-CT-based quantitative analysis tool that can measure the architectural impact of metastatic involvement in whole vertebrae. Micro-CT analysis of rat whole vertebrae was conducted using a combination of demons deformable registration, level set curvature evolution, and intensity based thresholding techniques along with upsampling and edge enhancement techniques. The algorithm was applied to 6 lumbar vertebrae (L1-3) from 6 rnu/rnu rats (3 healthy rats and 3 with metastatic involvement). Osteolytic metastatic involvement was modeled via MT1 human breast cancer cells. Excellent volumetric concurrency was achieved in comparing the automated micro-CT-based segmentations of the whole vertebrae, trabecular centrums, and individual trabecular networks to manual segmentations (98.9%, 96.1%, and 98.3%, respectively; 6 specimens), and the automated segmentations were achieved in a fraction of the time. The algorithm successfully accounted for discontinuities in the cortical shell caused by vasculature and osteolytic destruction. As such, this work demonstrates the potential of this highly automated segmentation tool to permit rapid precise quantitative structural analysis of the spine with minimum user interaction in the analysis of both healthy and pathological (metastatically involved) vertebrae. Future optimization and the incorporation of lower-resolution imaging parameters may allow automated analysis of clinical CT-based measures in addition to preclinical micro-CT-based analyses of the structural impact and progression of pathological processes in the spine.

Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease‐modifying antirheumatic drug treatment and correlation with radiologic outcome

To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet. Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3-6-month intervals after starting treatment with a disease-modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer-assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method. Thirteen patients achieved a low disease state as defined by a disease activity score <2.6 while 19 patients achieved an American College of Rheumatology response >20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet. Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.