Ampholytic ion-exchange magnetic beads: a promising tool for selecting short fragments in circulating cell-free DNA analysis.

Objective: For liquid biopsy of cancer, the extraction of circulating cell-free DNA (cfDNA) from plasma is required. We evaluated the efficacy of use of magnetic submicron particles coated with abundant small zwitterions (MSP-ZEWBs) for extracting short fragments of cfDNA. Methods: We developed and optimized an MSP-ZEWB-based cfDNA extraction method using ampholytic ion-exchange materials and compared its results with those using a control kit. We measured the cfDNA concentration by quantitative polymerase-chain-reaction and using the Qubit method and analyzed cfDNA fragmentation patterns using a bioanalyzer. Results: The fragment size of cfDNA isolated from glycine hydrochloric acid at a pH of 2.2 exhibited a better alignment with the DNA marker. The highest DNA intensity was observed at the final concentration of 0.8% polyethylene glycol 8000. The intensity of cfDNA decreased significantly when isolated from plasma with DNA marker using MSP-ZEWBs with an adsorption buffer containing guanidine hydrochloride or isothiocyanoguanidine. All fragments were successfully extracted using MSP-ZEWBs from both plasma and phosphate-buffered saline. Notably, the intensity of short cfDNA fragments isolated using MSP-ZEWBs remained consistent for recovery of long DNA fragments. indicating a potential selective of small fragments. Conclusion: The extraction of plasma cfDNA with MSP-ZEWBs requires no protein denaturation, shows resistance to cells remaining in plasma, and demonstrates higher overall efficiency and better reproducibility than other extraction methods. Use of MSP-ZEWBs may greatly enhance liquid biopsy of cancers through the analysis of plasma cfDNA in clinical practice.

The alternative splicing of intersectin 1 regulated by PTBP1 promotes human glioma progression.

Intersectin 1 (ITSN1) contains two isoforms: ITSN1-S and ITSN1-L, which are highly regulated by alternative splicing. Our previous results showed that the two isoforms of ITSN1 displayed opposite functions: ITSN1-S promoted glioma development, while ITSN1-L exerted an inhibitory role in glioma progression. In this study, our transcriptome analysis using a large glioma cohort indicated that the ratio of ITSN1-S/ITSN1-L was positively correlated with glioma grading and poor prognosis. We identified the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) as an ITSN1 pre-mRNA interaction protein through RNA pull-down assay and RNA immunoprecipitation assay. Knockdown of PTBP1 decreased the ratio of ITSN1-S/ITSN1-L. Minigene reporter assay and mutation analyses further confirmed PTBP1 targeted polypyrimidine sequences on ITSN1 exon 30 (TTGCACTTCAGTATTTT) and promoted the inclusion of ITSN1 exon 30. Subsequently, silencing PTBP1 inhibited glioma cell proliferation, migration, and invasion by down-regulating the ratio of ITSN1-S/ITSN1-L. Taken together, our study provides a novel mechanism that PTBP1 modulates the alternative splicing of ITSN1 and promotes glioma proliferation and motility by up-regulating the ratio of ITSN1-S/ITSN1-L, thereby highlighting that PTBP1 may be an attractive therapeutic target for gliomas.

Investigation of annular pancreas through multiple detector spiral CT (MDCT) and MRI.

BACKGROUND AND PURPOSE: To investigate annular pancreas in adults using imaging features displayed on computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: Retrospective review of annular pancreas in patients undergoing CT or MRI examinations. Two abdominal radiologists blindly reviewed the CT, MRI, and magnetic resonance cholangiopancreatography (MRCP) images from the Picture Archiving and Communication Systems (PACS). A Kruskal-Wallis test was performed to evaluate subjective scoring, with Mann-Whitney test for the comparison. A p-value less than 0.05 was considered statistically significant. RESULTS: Eleven patients (45.8%) presented a complete ring of pancreatic tissue surrounding duodenum, displayed as circular, triangular, or sandwich sign configuration, the other 13 patients (54.2%) had incomplete annular pancreas which displayed a crocodile jaw appearance, pancreatic tissue extending in a posterolateral or anterolateral direction towards duodenum. When comparing CT images of each sequence, the arterial phase group had the highest score compared with the venous phase and the plain film group (χ2  = 58.21, p < 0.05). When comparing MRI enhancement volumetric interpolated breath-hold examination (VIBE) sequences, arterial phase group scores were the highest (χ2  = 18.98, p < 0.05). CONCLUSIONS: Both CT and MRI could detect annular pancreas, with artery phase being the best sequence to diagnose annular pancreas.

Pan-cancer analyses reveal IGSF10 as an immunological and prognostic biomarker.

Background: IGSF10 is a member of the immunoglobulin superfamily. Over the previous decade, growing proof has validated definitive correlations between individuals of the immunoglobulin superfamily and human diseases. However, the function of IGSF10 in pan-cancer stays unclear. We aimed to analyze the immunological and prognostic value of IGSF10 in pan-cancer. Methods: We utilized a vary of bioinformatic ways to inspect the function of IGSF10 in pan-cancer, including its correlation with prognosis, immune cell infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferases, genetic alteration, drug sensitivity, etc. Results: We noticed low expression of IGSF10 in most cancer types. IGSF10 expression in tumor samples correlates with prognosis in most cancers. In most cancer types, IGSF10 expression was strongly related to immune cells infiltration, immune checkpoints, immune modulators, TMB, MSI, MMR, and DNA methyltransferases, among others. Functional enrichment analyses indicated that IGSF10 expression was involved in lymphocyte differentiation, cell molecules adhesion, etc. Furthermore, low IGSF10 expression could increase the drug sensitivity of many drugs. Conclusion: IGSF10 could serve as a novel prognostic marker and attainable immunotherapy target for several malignancies.

Detection of Cervical Cancer Cells in Whole Slide Images Using Deformable and Global Context Aware Faster RCNN-FPN.

Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN architecture for the detection of abnormal cervical cells in cytology images from a cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cervical image dataset of "Digital Human Body" Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using traditional computer-vision techniques, 6-9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear.

Salient Object Detection Based on Visual Perceptual Saturation and Two-Stream Hybrid Networks.

Inspired by the perceived saturation of human visual system, this paper proposes a two-stream hybrid networks to simulate binocular vision for salient object detection (SOD). Each stream in our system consists of unsupervised and supervised methods to form a two-branch module, so as to model the interaction between human intuition and memory. The two-branch module parallel processes visual information with bottom-up and top-down SODs, and output two initial saliency maps. Then a polyharmonic neural network with random-weight (PNNRW) is utilized to fuse two-branch's perception and refine the salient objects by learning online via multi-source cues. Depend on visual perceptual saturation, we can select optimal parameter of superpixel for unsupervised branch, locate sampling regions for PNNRW, and construct a positive feedback loop to facilitate perception saturated after the perception fusion. By comparing the binary outputs of the two-stream, the pixel annotation of predicted object with high saturation degree could be taken as new training samples. The presented method constitutes a semi-supervised learning framework actually. Supervised branches only need to be pre-trained initial, the system can collect the training samples with high confidence level and then train new models by itself. Extensive experiments show that the new framework can improve performance of the existing SOD methods, that exceeds the state-of-the-art methods in six popular benchmarks.

Cohort study of chest CT and clinical changes in 29 patients with coronavirus disease 2019 (COVID-19).

OBJECTIVES: To investigate the imaging findings and clinical time course of COVID-19 pneumonia. METHODS: A total of 113 baseline and follow-up CT scans from 24 January 2020 to 18 February 2020 were longitudinally collected from 29 confirmed COVID-19 patients in a single center. The changes in the clinical and laboratory characteristics, imaging features, lesion-to-muscle ratio (LMR), and pulmonary inflammation index (PII) at baseline, 1-6 days, 7-13 days, and ≥ 14 days were compared. RESULTS: Of the 29 COVID-19 patients enrolled, the baseline chest CT scan was obtained 3 ± 2 (0-9) days after the onset of symptoms, and each patient had an average of 4 ± 1 (3-5) CT scans with a mean interval of 5 ± 2 (1-14) days. The percentage of patients with fever, cough, shortness of breath, and myalgia obviously decreased at 7-13 days with regular treatment (p < 0.05). The lymphocyte count, C-reactive protein, interleukin-6, and oxygenation index worsened within 1-6 days but improved sharply at 7-13 days. Compared with those at the other three time points, the LMR, PII, and number of involved lobes at 1-6 days were the highest, and gradually improved after 7-13 days. CONCLUSIONS: Lung lesion development on chest CT reflects the clinical time course of COVID-19 progression over 1-6 days, followed by clinical improvement and the resorption of lesions. CT imaging may be indicated when patients fail to improve within a week of treatment, but repeated chest CT may be unnecessary when the patients show improvements clinically. KEY POINTS: • Chest CT reflects the development of coronavirus disease 2019 pneumonia (COVID-19). • COVID-19 usually shows progressive lesions over up to 9 days with subsequent resorption. • Unusual clinical time course of COVID-19 may indicate repeated chest CT.

Classification of breast cancer histopathological images using interleaved DenseNet with SENet (IDSNet).

In this study, we proposed a novel convolutional neural network (CNN) architecture for classification of benign and malignant breast cancer (BC) in histological images. To improve the delivery and use of feature information, we chose the DenseNet as the basic building block and interleaved it with the squeeze-and-excitation (SENet) module. We conducted extensive experiments with the proposed framework by using the public domain BreakHis dataset and demonstrated that the proposed framework can produce significantly improved accuracy in BC classification, compared with the state-of-the-art CNN methods reported in the literature.

[Expression of MiRNA-19a in Cells of Multiple Myeloma Patients and Its Effect on the Characteristics of Myeloma Cells].

OBJECTIVE: To detect the expression level of miR-19a, one of the oncogenic miR-17-92 cluster, in multiple myeloma cell lines Lp-1 and U266 in vitro and to explore the effects of miR-19a on biological behavior, such as proliferation, migration and apoptosis of Lp-1 and U266 myeloma cells by transfection with miR-19a mimic through LipofectamineTM2000. METHODS: The reverse transcription-PCR was applied to detect the expression level of miR-19a in multiple myeloma cell lines Lp-1 and U266 in vitro. The CCK8 was used to assay the effect of miR-19a on the proliferation of Lp-1 and U266 cells in vitro, the transwell migration test was adopted to determine the effect of up-regulation of miR-19a on the migration of Lp-1 and U266 multiple myeloma cells in vitro. The flow cytometry was used to detect the effect of miR-19a on the apoptosis of Lp-1 and U266 cells in vitro. RESULTS: The miR-19a expression was higher in Lp-1 and U266 multiple myeloma cells; compared with the transfected cells with a specific miR-19a NC, those samples transfected with miR-19a mimic displayed significantly higher expression of miR-19a (P<0.05), indicating a higher transfection efficiency; the miR-19a could promote the proliferation of Lp-1 and U266 multiple myeloma cells in vitro. MiR-19a could promote migration ability of Lp-1 and U266 multiple myeloma cell lines in vitro and could inhibit the apoptosis of Lp-1 and U266 cells. CONCLUSION: miR-19a is overexpressed significantly in Lp-1 and U266 multiple myeloma cells, and promots the proliferation and invasion of the myeloma cells, but inhibits their apoptosis.

Tau and Pet/Mri Imaging Biomarkers for Detecting and Diagnosing Early Dementia.

Specific objective of this project is to quantify the neuropathological tau depositions in brain regions and to investigate primary age-related tau pathology and associations with amyloid and glucose-metabolism, neurocognitive tests and MRI metrics. Preliminary results demonstrated higher temporal deposition especially in the hippocampus and the inferior temporal regions compared to mean cortical deposition. Quantitative Braak stage-based regional analyses found highest tau deposition in the Braak stage II in the preclinical samples. There was significant age related higher tau deposition in temporal cortex, while non-significant correlation in mean cortical region. Significant correlations were found between tau deposition and memory as well as executive function scores, especially from middle and inferior temporal cortex; and significant correlations between tau and MRI metrics including diffusion, perfusion, functional and structural connectivities. Our results confirm current notion of this new tau tracer for reliably and consistently labeling and quantifying in vivo human taupathy in early dementia.

p53 Deletion promotes myeloma cells invasion by upregulating miR19a/CXCR5.

P53 deletion has been identified as one of the few factors that defined high risk and poor prognosis in MM. It has been reported p53 deletion is associated with resistance to chemotherapy and organ infiltrations of MM. However, p53 deletion in the migration and dissemination of MM cells has not been totally elucidated. In this research, first, we investigated whether p53 is associated with migration of MM cells. We found that p53 regulates the migration of NCI-H929 cells with wild-type p53 but not U266 cells with mutated-type p53. Next, we investigated the related mechanism by which p53 regulates the migration. We found that down-regulation of p53 reduced adhesion of NCI-H929 cells to the BM stroma via decreased expression of E-cadherin and increased EMT-regulating proteins. Further study have identified the miR-19a/CXCR5 pathway as a candidate p53-induced migration mechanism. In conclusion, we have demonstrated for the first time the critical value of p53 deletion in MM cell migration and dissemination, as well as the acquisition of an EMT-like phenotype. Our research provides new insights into the function of p53 in migration of MM and suggests p53/miRNA19a/CXCR5 may provide potentially therapeutic targets for the treatment of myeloma with p53 deletion.

Abnormal structural and functional hypothalamic connectivity in mild traumatic brain injury.

PURPOSE: To investigate whether there is imaging evidence of hypothalamic injury in patients with mild traumatic brain injury (MTBI), which is a major public health problem due to the high prevalence and difficulty in diagnosis and treatment. MATERIALS AND METHODS: Twenty-four patients (mean age 34.2, range, 18-56 years) with symptomatic MTBI and 22 age-matched healthy controls (mean age 37.0, range 20-61 years) participated in the study. Diffusion kurtosis imaging was performed with diffusion-weighted images acquired along 30 gradient directions and three b-values (b = 0, 1000, 2000 s/mm2 ) based on a twice-refocused spin-echo sequence with a 3T magnetic resonance imaging (MRI) scanner. Resting-state functional (f)MRI with standard echo planar imaging (EPI) were performed to localize the resting-state networks (RSN) and hypothalamic functional connectivity. RESULTS: There were significantly reduced mean kurtosis (P = 0.0092) and radial kurtosis (P = 0.0078) in patients as compared to controls in the hypothalamus. Furthermore, there was a significant negative correlation (r = -0.675, P = 0.0007) between radial kurtosis in the hypothalamus and fatigue severity scale in patients. The MTBI group also showed disrupted hypothalamic RSNs, with significantly decreased positive connectivity in medial prefrontal cortex, inferior posterior parietal, and cingulate regions but increased connectivity in the peri-hypothalamic regions and cerebellum, together with significantly decreased negative RSNs in visual and bilateral premotor areas (cluster corrected P < 0.05). CONCLUSION: Our results show disruption of functional and structural hypothalamic connectivity in patients with MTBI, and might further the understanding of an array of clinical symptoms in MTBI such as sleep disturbance and fatigue. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1105-1112.

Small world properties changes in mild traumatic brain injury.

PURPOSE: To investigate local and global efficiency changes characterized by small-world properties based on resting-state functional MRI, such as centrality and clustering coefficient, in mild traumatic brain injury (MTBI) patients; and to associate these findings with axonal injury as measured by diffusion tensor imaging (DTI) as well as with post-concussive symptom (PCS). MATERIALS AND METHODS: Thirty patients (mean age 35 ± 13 years) with clinically defined MTBI and 45 age-matched healthy controls (mean age 37 ± 10 years) participated in the experiments. Resting-state functional MRI was performed using gradient echo planar imaging sequence with 3 Tesla MRI scanner to obtain functional small-world networks. Out of all participants, 20 MTBI patients and 20 controls had available DTI data with three b-values (0, 500, 1000) s/mm2 and 30 directions for diffuse axonal injury analyses. RESULTS: Compared with controls, MTBI patients showed lower relative betweenness centrality (P = 0.01), but significantly higher clustering coefficient (P = 0.04), and these two metrics correlated negatively in patients (r = -0.77; P < 0.001). Regions with lower betweenness centrality (e.g., frontal and occipital) corresponded with the regions of reduced FA in patients, while global FA reduction correlated with betweenness centrality (r = 0.48; P = 0.03) and clustering coefficient (r = -0.46; P = 0.04) in MTBI patients. In addition, there was significantly higher thalamocortical connectivity that correlated with clustering coefficient (r = 0.39; P = 0.03) in patients. Also, patients with higher clustering coefficient tended to have less PCS score with negative correlation (r = -0.4; P = 0.04). CONCLUSION: Our results demonstrated significant functional small-world properties changes in patients with MTBI, and suggest decreased global efficiency, possibly due to diffuse axonal injury and local network upregulation including increased thalamo-cortical connectivity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:518-527.

Quantitative PET/MRI Evaluation and Application in Dementia.

A recently introduced integrated scanner combining simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET/MRI) acquisition presents a unique set of opportunities for neuroimaging research and dementia in particular [1]. Among these, the intrinsic co-registration of the images has the potential to reduce errors in multi-modality image registration, which could lead to better quantification of longitudinal volumetric changes in neuroanatomical features that are important for assessing disease progression. PET tracers could provide functional information of brain biochemical processes by radio-labeling specific molecular with high sensitivity and specificity, while MRI could provide superior structural information. Applying MRI anatomical priors to reduce the PET partial volume effect is straightforward, and could further be used to improve spatial resolution of PET images [2]. The hardware challenge in integrating PET and MRI system is the interaction of the PET electronics and MRI system [3]. The special deign of the PET/MRI-PET detector (so called "MR transparent") architecture includes integrated cooling features to assure optimal PET performance, as well as specialized shielding to virtually eliminate magnetic field interference in the PET data processing chain [4]. On the MRI side, larger bore size with cylindrically optimized homogeneity volume has been used for better image quality [4]. Another challenge of the PET/MRI scanner is the derivation of attenuation correction (AC) from MRI for PET images reconstruction [2]. Three commonly-used MR-based AC (MRAC) methods had been proposed: template-based MRAC, Dixon's method [5] for fat/water separation which assigns AC values based on the segmentation of fat, water and relative bone tissues, as well as dual-echo or multi-echo ultra-short TE (UTE) MRI sequence [6] for delineation of bone, air and software tissue.

Effects of age and smoking on endothelial function assessed by quantitative cardiovascular magnetic resonance in the peripheral and central vasculature.

BACKGROUND: Both age and smoking promote endothelial dysfunction and impair vascular reactivity. Here, we tested this hypothesis by quantifying new cardiovascular magnetic resonance (CMR)-based biomarkers in smokers and nonsmokers. METHODS: Study population: young non-smokers (YNS: N = 45, mean age = 30.2 ± 0.7 years), young smokers (YS: N = 39 mean age 32.1 ± 0.7 years), older non-smokers (ONS: N = 45, mean age = 57.8 ± 0.6 years), and older smokers (OS: N = 40, mean age = 56.3 ± 0.6 years), all without overt cardiovascular disease. Vascular reactivity was evaluated following cuff-induced hyperemia via time-resolved blood flow velocity and oxygenation (SvO2) in the femoral artery and vein, respectively. SvO2 dynamics yielded washout time (time to minimum SvO2), resaturation rate (upslope) and maximum change from baseline (overshoot). Arterial parameters included pulse ratio (PR), hyperemic index (HI) and duration of hyperemia (TFF). Pulse-wave velocity (PWV) was assessed in aortic arch, thoracoabdominal aorta and iliofemoral arteries. Ultrasound-based carotid intimal-medial thickness (IMT) and brachial flow-mediated dilation were measured for comparison. RESULTS: Age and smoking status were independent for all parameters. Smokers had reduced upslope (-28.4%, P < 0.001), increased washout time (+15.3%, P < 0.01), and reduced HI (-19.5%, P < 0.01). Among non-smokers, older subjects had lower upslope (-22.7%, P < 0.01) and overshoot (-29.4%, P < 0.01), elevated baseline pulse ratio (+14.9%, P < 0.01), central and peripheral PWV (all P < 0.05). Relative to YNS, YS had lower upslope (-23.6%, P < 0.01) and longer washout time (13.5%, P < 0.05). Relative to ONS, OS had lower upslope (-33.0%, P < 0.01). IMT was greater in ONS than in YNS (+45.6%, P < 0.001), and also in YS compared to YNS (+14.7%, P < 0.05). CONCLUSIONS: Results suggest CMR biomarkers of endothelial function to be sensitive to age and smoking independent of each other.

Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques.

PURPOSE: To compare cerebrovascular reactivity (CVR) quantified with pseudo-continuous arterial spin labeling (pCASL) and blood oxygen level dependent (BOLD) fMRI techniques. MATERIALS AND METHODS: Sixteen healthy volunteers (age: 37.8±14.3years; 6 women and 10 men; education attainment: 17±2.1years) were recruited and completed a 5% CO2 gas-mixture breathing paradigm at 3T field strength. ASL and BOLD images were acquired for CVR determination assuming that mild hypercapnia does not affect the cerebral metabolic rate of oxygen. Both CVR quantifications were derived as the ratio of the fractional cerebral blood flow (CBF) or BOLD signal change over the change in end-tidal CO2 pressure. RESULTS: The absolute CBF, BOLD and CVR measures were consistent with literature values. CBF derived CVR was 5.11±0.87%/mmHg in gray matter (GM) and 4.64±0.37%/mmHg in parenchyma. BOLD CVR was 0.23±0.04%/mmHg and 0.22±0.04%/mmHg for GM and parenchyma respectively. The most significant correlations between BOLD and CBF-based CVRs were also in GM structures, with greater vascular response in occipital cortex than in frontal and parietal lobes (6.8%/mmHg versus 4.5%/mmHg, 50% greater). Parenchymal BOLD CVR correlated significantly with the fractional change in CBF in response to hypercapnia (r=0.61, P=0.01), suggesting the BOLD response to be significantly flow driven. GM CBF decreased with age in room air (-5.58mL/100g/min per decade for GM; r=-0.51, P=0.05), but there was no association of CBF with age during hypercapnia. A trend toward increased pCASL CVR with age was observed, scaling as 0.64%/mmHg per decade for GM. CONCLUSION: Consistent with previously reported CVR values, our results suggest that BOLD and CBF CVR techniques are complementary to each other in evaluating neuronal and vascular underpinning of hemodynamic processes.

White matter lesion load is associated with resting state functional MRI activity and amyloid PET but not FDG in mild cognitive impairment and early Alzheimer's disease patients.

PURPOSE: To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. MATERIALS AND METHODS: Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [(18)F]-Florbetapir tracer and metabolism of glucose by means of [(18)F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). RESULTS: Whole-brain WMLL and amyloid deposition were significantly higher (P < 0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P < 0.05) DMN connectivity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P < 0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. CONCLUSION: Our quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Significant correlations between MRI metrics, including WMLL/functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD.

Multiparametric MRI characterization and prediction in autism spectrum disorder using graph theory and machine learning.

This study employed graph theory and machine learning analysis of multiparametric MRI data to improve characterization and prediction in autism spectrum disorders (ASD). Data from 127 children with ASD (13.5±6.0 years) and 153 age- and gender-matched typically developing children (14.5±5.7 years) were selected from the multi-center Functional Connectome Project. Regional gray matter volume and cortical thickness increased, whereas white matter volume decreased in ASD compared to controls. Small-world network analysis of quantitative MRI data demonstrated decreased global efficiency based on gray matter cortical thickness but not with functional connectivity MRI (fcMRI) or volumetry. An integrative model of 22 quantitative imaging features was used for classification and prediction of phenotypic features that included the autism diagnostic observation schedule, the revised autism diagnostic interview, and intelligence quotient scores. Among the 22 imaging features, four (caudate volume, caudate-cortical functional connectivity and inferior frontal gyrus functional connectivity) were found to be highly informative, markedly improving classification and prediction accuracy when compared with the single imaging features. This approach could potentially serve as a biomarker in prognosis, diagnosis, and monitoring disease progression.

Characterization of thalamo-cortical association using amplitude and connectivity of functional MRI in mild traumatic brain injury.

PURPOSE: To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). MATERIALS AND METHODS: Twenty-seven patients and 27 age-matched controls were recruited. The 3 Tesla fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01-0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. RESULTS: In comparison with controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption also existed at task-related condition in patients. CONCLUSION: The decreased fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide additional evidence of thalamic injury in patients with MTBI. Our findings of fALFFs and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI.