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An abscopal response describes radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field. Granulocyte-macrophage colony-stimulating factor is a potent stimulator of dendritic cell maturation. We postulated that the exploitation of the pro-immunogenic effects of radiotherapy with granulocyte-macrophage colony-stimulating factor might result in abscopal responses among patients with metastatic cancer. Patients with stable or progressing metastatic solid tumours, on single-agent chemotherapy or hormonal therapy, with at least three distinct measurable sites of disease, were treated with concurrent radiotherapy (35 Gy in ten fractions, over 2 weeks) to one metastatic site and granulocyte-macrophage colony-stimulating factor (125 μg/m2 subcutaneously injected daily for 2 weeks, starting during the second week of radiotherapy). This course was repeated, targeting a second metastatic site. A Simon's optimal two-stage design was chosen for this trial: an additional 19 patients could be enrolled in stage 2 only if at least one patient among the first ten had an abscopal response. If no abscopal responses were seen among the first ten patients, the study would be deemed futile and terminated. The primary endpoint was the proportion of patients with an abscopal response (defined as at least a 30% decrease in the longest diameter of the best responding abscopal lesion). Secondary endpoints were safety and survival. Analyses were done based on intention to treat. The trial has concluded accrual, and is registered with ClinicalTrials.gov, number NCT02474186. From April 7, 2003, to April 3, 2012, 41 patients with metastatic cancer were enrolled. In stage 1 of the Simon's two-stage design, ten patients were enrolled: four of the first ten patients had abscopal responses. Thus, the trial proceeded to stage 2, as planned, and an additional 19 patients were enrolled. Due to protocol amendments 12 further patients were enrolled. Abscopal responses occurred in eight (27·6%, 95% CI 12·7–47·2) of the first 29 patients, and 11 (26·8%, 95% CI 14·2–42·9) of 41 accrued patients (specifically in four patients with non-small-cell lung cancer, five with breast cancer, and two with thymic cancer). The most common grade 3–4 adverse events were fatigue (six patients) and haematological (ten patients). Additionally, a serious adverse event of grade 4 pulmonary embolism occurred in one patient. The combination of radiotherapy with granulocyte-macrophage colony-stimulating factor produced objective abscopal responses in some patients with metastatic solid tumours. This finding represents a promising approach to establish an in-situ anti-tumour vaccine. Further research is warranted in this area. New York University School of Medicine's Department of Radiation Oncology and Cancer Institute.

Magnetic resonance imaging (MRI) has been proposed as a complimentary method to measure bone quality and assess fracture risk. However, manual segmentation of MR images of bone is time-consuming, limiting the use of MRI measurements in the clinical practice. The purpose of this paper is to present an automatic proximal femur segmentation method that is based on deep convolutional neural networks (CNNs). This study had institutional review board approval and written informed consent was obtained from all subjects. A dataset of volumetric structural MR images of the proximal femur from 86 subjects were manually-segmented by an expert. We performed experiments by training two different CNN architectures with multiple number of initial feature maps, layers and dilation rates, and tested their segmentation performance against the gold standard of manual segmentations using four-fold cross-validation. Automatic segmentation of the proximal femur using CNNs achieved a high dice similarity score of 0.95 ± 0.02 with precision = 0.95 ± 0.02, and recall = 0.95 ± 0.03. The high segmentation accuracy provided by CNNs has the potential to help bring the use of structural MRI measurements of bone quality into clinical practice for management of osteoporosis.

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (ρ=0.66; p=0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (ρ=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter. •We monitored de- and remyelination with compartment-specific diffusion MRI metrics.•Axonal water fraction decreased with patchy demyelination (6weeks of cuprizone).•Extra-axonal radial diffusivity increased with widespread demyelination (12weeks).•Correlations with electron microscopy supported each metric's specificity.•These metrics are promising candidates as clinical biomarkers of demyelination.

Abstract Rationale Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer’s disease. However, how sleep apnea affects longitudinal risk for Alzheimer’s disease is less well understood. Objectives To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Methods Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. Measurements and Main Results We found that severity of OSA indices (AHIall [F  1,88 = 4.26; P < 0.05] and AHI4% [F  1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F  1,28 = 2.96, P = 0.09; and F  1,28 = 2.32, not significant, respectively). Conclusions In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (mTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in mTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of mTBI patients, and can help ascertain if thalamic injury is associated with cognitive impairment. Twenty-two mTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within 1 year after injury exhibited variously altered DTI- and DKI-derived measures in the thalamus and the internal capsule, while in addition to these regions, patients examined more than 1 year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated with MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome.

Purpose The purpose of this study was to evaluate the diagnostic performance of a “simulated” abbreviated MRI (AMRI) protocol using diffusion-weighted imaging (DWI) and T1-weighted (T1w) imaging obtained at the hepatobiliary phase (HBP) post gadoxetic acid injection alone and in combination, compared to dynamic contrast-enhanced (CE)-T1w imaging for the detection of hepatocellular carcinoma (HCC). Methods This was an IRB approved HIPAA compliant retrospective single institution study including patients with liver disease who underwent gadoxetic acid-enhanced MRI for HCC diagnosis. Three independent observers assessed 2 sets of images (full CE-set and AMRI including DWI+T1w-HBP). Diagnostic performance of T1w-HBP and DWI alone and in combination was compared to that of CE-set. All imaging sets included unenhanced T1w and T2w sequences. A preliminary analysis was performed to assess cost savings of AMRI protocol compared to a full MRI study. Results 174 patients including 62 with 80 HCCs were assessed. Equivalent per-patient sensitivity and negative predictive value (NPV) were observed for DWI (85.5% and 92.2%, pooled data) and T1w-HBP (89.8% and 94.2%) ( P  = 0.1–0.7), while these were significantly lower for the full AMRI protocol (DWI+T1w-HBP, 80.6% and 80%, P  = 0.02) when compared to CE-set (90.3% and 94.9%). Higher specificity and positive predictive value were observed for CE-set vs. AMRI ( P  = 0.02). The estimated cost reduction of AMRI versus full MRI ranged between 30.7 and 49.0%. Conclusion AMRI using DWI and T1w-HBP has a clinically acceptable sensitivity and NPV for HCC detection. This could serve as the basis for a future study assessing AMRI for HCC screening and surveillance.

Objectives To evaluate a dynamic half-Fourier acquired single turbo spin echo (HASTE) sequence following anterior cervical discectomy and fusion (ACDF) at the junctional level for adjacent segment degeneration comparing dynamic listhesis to radiographs and assessing dynamic cord contact and deformity during flexion-extension Methods Patients with ACDF referred for cervical spine MRI underwent a kinematic flexion-extension sagittal 2D HASTE sequence in addition to routine sequences. Images were independently reviewed by three radiologists for static/dynamic listhesis, and compared to flexion-extension radiographs. Blinded assessment of the HASTE sequence was performed for cord contact/deformity between neutral, flexion, and extension, to evaluate concordance between readers and inter-modality agreement. Inter-reader agreement for dynamic listhesis and impingement grade and inter-modality agreement for dynamic listhesis on MRI and radiographs was assessed using the kappa coefficient and percentage concordance. Results A total of 28 patients, mean age 60.2 years, were included. Mean HASTE acquisition time was 42 s. 14.3% demonstrated high grade dynamic stenosis ( > grade 4) at the adjacent segment. There was substantial agreement for dynamic cord impingement with 70.2% concordance (kappa = 0.62). Concordance across readers for dynamic listhesis using HASTE was 81.0% (68/84) (kappa = 0.16) compared with 71.4% (60/84) (kappa = 0.40) for radiographs. Inter-modality agreement between flexion-extension radiographs and MRI assessment for dynamic listhesis across the readers was moderate (kappa = 0.41; 95% confidence interval: 0.16 to 0.67). Conclusions A sagittal flexion-extension HASTE cine sequence provides substantial agreement between readers for dynamic cord deformity and moderate agreement between radiographs and MRI for dynamic listhesis. Clinical relevance statement Degeneration of the adjacent segment with instability and myelopathy is one of the most common causes of pain and neurological deterioration requiring re-operation following cervical fusion surgery. Key Points • A real-time kinematic 2D sagittal HASTE flexion-extension sequence can be used to assess for dynamic listhesis, cervical cord, contact and deformity. • The additional kinematic cine sequence was well tolerated and the mean acquisition time for the 2D HASTE sequence was 42 s (range 31–44 s). • A sagittal flexion-extension HASTE cine sequence provides substantial agreement between readers for dynamic cord deformity and moderate agreement between radiographs and MRI for dynamic listhesis.

•Hippocampal Glx correlated with CSF p-tau181, but not after covariate adjustment.•Hippocampal NAA correlated with volume, even after covariate adjustment.•Both correlations were driven by APOE4 carriers.•There were no correlations in regions affected at later Braak stages (IV-VI). The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC. [Display omitted]

Background To assess the performance of imaging features, including radiomics texture features, in predicting histopathologic tumor grade, AJCC stage, and outcomes [time to recurrence (TTR) and overall survival (OS)] in patients with intrahepatic cholangiocarcinoma (ICC). Methods Seventy-three patients (26 M/47F, mean age 63y) with pre-operative imaging (CT, n  = 37; MRI, n  = 21; CT and MRI, n  = 15] within 6 months of resection were included in this retrospective study. Qualitative imaging traits were assessed by 2 observers. A 3rd observer measured tumor apparent diffusion coefficient (ADC), enhancement ratios (ERs), and Haralick texture features. Blood biomarkers and imaging features were compared with histopathology (tumor grade and AJCC stage) and outcomes (TTR and OS) using log-rank, generalized Wilcoxon, Cox proportional hazards regression, and Fisher exact tests. Results Median TTR and OS were 53.9 and 79.7 months. ICC recurred in 64.4% (47/73) of patients and 46.6% (34/73) of patients died. There was fair accuracy for some qualitative imaging features in the prediction of worse tumor grade (maximal AUC of 0.68 for biliary obstruction on MRI, p  = 0.032, observer 1) and higher AJCC stage (maximal AUC of 0.73 for biliary obstruction on CT, p  = 0.002, observer 2; and AUC of 0.73 for vascular involvement on MRI, p  = 0.01, observer 2). Cox proportional hazards regression analysis showed that CA 19–9 [hazard ratio (HR) 2.44/95% confidence interval (CI) 1.31–4.57/ p  = 0.005)] and tumor size on imaging (HR 1.13/95% CI 1.04–1.22/ p  = 0.003) were significant predictors of TTR, while CA 19–9 (HR 4.08/95% CI 1.75–9.56, p  = 0.001) and presence of metastatic lymph nodes at histopathology (HR 2.86/95% CI 1.35–6.07/ p  = 0.006) were significant predictors of OS. On multivariable analysis, satellite lesions on CT (HR 2.79/95%CI 1.01–7.15/ p  = 0.032, observer 2), vascular involvement on MRI (HR 0.10/95% CI 0.01–0.85/ p  = 0.032, observer 1), and texture feature MRI variance (HR 0.55/95% CI 0.31–0.97, p  = 0.040) predicted TTR once adjusted for the independent predictors CA 19–9 and tumor size on imaging. Several qualitative and quantitative features demonstrated associations with TTR, OS, and AJCC stage at univariable analysis (range: HR 0.35–19; p  < 0.001–0.045), however none were predictive of OS at multivariable analysis when adjusted for CA 19–9 and metastatic lymph nodes ( p  > 0.088). Conclusions There was reasonable accuracy in predicting tumor grade and higher AJCC stage in ICC utilizing certain qualitative and quantitative imaging traits. Serum CA 19–9, tumor size, presence of metastatic lymph nodes, and qualitative imaging traits of satellite lesions and vascular involvement are predictors of patient outcomes, along with a promising predictive ability of certain quantitative texture features.

Objectives To assess whether MR fingerprinting (MRF)–based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. Methods Clinical imaging, MRF, and DTI were acquired in patients (24 ± 10 days after injury (timepoint 1) and 90 ± 17 days after injury (timepoint 2)) and once in controls. Patient outcome was assessed with global functioning, symptom profile, and neuropsychological testing. ADC and fractional anisotropy (FA) from DTI and T 1 and T 2 from MRF were compared in 12 gray and white matter regions with Mann–Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. Results Data from 22 patients (38 ± 12 years; 17 women) and 18 controls (32 ± 8 years; 12 women) were analyzed. Fourteen patients (37 ± 12 years; 11 women) returned for timepoint 2, while two patients provided only timepoint 2 clinical outcome data. At timepoint 1, there were no differences between patients and controls in T 1 , T 2 , and ADC, while FA was lower in mTBI frontal white matter. T 1 at timepoint 1 and the change in T 1 exhibited more ( n  = 18) moderate to strong correlations (| r |= 0.6–0.85) with clinical outcome at timepoint 2 than T 2 ( n  = 3), FA ( n  = 7), and ADC ( n  = 2). High T 1 at timepoint 1, and serially increasing T 1 , accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). Conclusion T 1 derived from MRF was found to have higher utility than T 2 , FA, and ADC for predicting 3-month outcome after mTBI. Key Points • In a region-of-interest approach, FA, ADC, and T 1 and T 2 all showed limited utility in differentiating patients from controls at an average of 24 and 90 days post-mild traumatic brain injury. • T 1 at 24 days, and the serial change in T 1 , revealed more and stronger predictive correlations with clinical outcome at 90 days than did T 2 , ADC, or FA. • T 1 showed better prospective identification of non-recovered patients at 90 days than ADC, T 2 , and FA.