An interpretable machine learning model to explain the interplay between brain lesions and cortical atrophy in multiple sclerosis.

Multiple Sclerosis (MS) is the most common cause, (after trauma) of neurological disability in young adults in Western countries. While several Magnetic Resonance Imaging (MRI) studies have demonstrated a strong association between the presence of cortical grey matter atrophy and the progression of neurological impairment in MS patients, the neurobiological substrates of cortical atrophy in MS, and in particular its relationship with white matter (WM) and cortical lesions, remain unknown. The aim of this study was to investigate the interplay between cortical atrophy and different types of lesions at Ultra-High Field (UHF) 7 T MRI, including cortical lesions and lesions with a susceptibility rim (a feature which histopathological studies have associated with impaired remyelination and progressive tissue destruction). We combined lesion characterization with a recent machine learning (ML) framework which includes explainability, and we were able to predict cortical atrophy in MS from a handful of lesion-related features extracted from 7 T MR imaging. This highlights not only the importance of UHF MRI for accurately evaluating intracortical and rim lesion load, but also the differential contributions that these types of lesions may bring to determine disease evolution and severity. Also, we found that a small subset of features [WM lesion volume (not considering rim lesions), patient age and WM lesion count (not considering rim lesions), intracortical lesion volume] carried most of the prediction power. Interestingly, an almost opposite pattern emerged when contrasting cortical with WM lesion load: WM lesion load is most important when it is small, whereas cortical lesion load behaves in the opposite way.Clinical Relevance- Our results suggest that disconnection and axonal degeneration due to WM lesions and local cortical demyelination are the main factors determining cortical thinning. These findings further elucidate the complexity of MS pathology across the whole brain and the need for both statistical and mechanistic approaches to understanding the etiopathogenesis of lesions.

High-resolution computed tomography evaluation of congenital aural atresia - how useful is this?

OBJECTIVE: To depict various temporal bone abnormalities on high-resolution computed tomography in congenital aural atresia patients, and correlate these findings with auditory function test results and microtia subgroup. METHODS: Forty patients (56 ears) with congenital malformation of the auricle and/or external auditory canal were evaluated. Auricles were graded according to Marx's classification, divided into subgroups of minor (grades I and II) and major (III and IV) microtia. Other associated anomalies of the external auditory canal, tympanic cavity, ossicular status, oval and round windows, facial nerve, and inner ear were evaluated. RESULTS: Minor and major microtia were observed in 53.6 and 46.4 per cent of ears respectively. Mean hearing levels were 62.47 and 62.37 dB respectively (p = 0.98). The malleus was the most commonly dysplastic ossicle (73.3 vs 80.8 per cent of ears respectively, p = 0.53). Facial nerve (mastoid segment) abnormalities were associated (p = 0.04) with microtia subgroup (80 vs 100 per cent in minor vs major subgroups). CONCLUSION: Microtia grade was not significantly associated with mean hearing levels or other ear malformations, except for external auditory canal and facial nerve (mastoid segment) anomalies. High-resolution computed tomography is essential in congenital aural atresia, before management strategy is decided.

Building Capacity for Evidence-Informed Priority Setting in the Indian Health System: An International Collaborative Experience.

India's rapid economic growth has been accompanied by slower improvements in population health. Given the need to reconcile the ambitious goal of achieving Universal Coverage with limited resources, a robust priority-setting mechanism is required to ensure that the right trade-offs are made and the impact on health is maximised. Health Technology Assessment (HTA) is endorsed by the World Health Assembly as the gold standard approach to synthesizing evidence systematically for evidence-informed priority setting (EIPS). India is formally committed to institutionalising HTA as an integral component of the EIPS process. The effective conduct and uptake of HTA depends on a well-functioning ecosystem of stakeholders adept at commissioning and generating policy-relevant HTA research, developing and utilising rigorous technical, transparent, and inclusive methods and processes, and a strong multisectoral and transnational appetite for the use of evidence to inform policy. These all require myriad complex and complementary capacities to be built at each level of the health system . In this paper we describe how a framework for targeted and locally-tailored capacity building for EIPS, and specifically HTA, was collaboratively developed and implemented by an international network of priority-setting expertise, and the Government of India.

Cancer with unknown primary: finding a needle in a hay stack.

Detection and resection of small neuroendocrine tumours (NET) is like finding a needle in a hay stack. Use of specific tracers such as (68)Ga-DOTATOC in a PET/CT study has been proven to have a high sensitivity and specificity to cells expressing somatostatin-SSR receptors. The use of (99m)Tc-Octreotide to detect neuroendocrine tumours during surgery is an effective adjunct for therapy. We here present a clinical case of patient with NET where these modalities help in both diagnostic and therapeutic surgery.

Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI.

PURPOSE: We evaluated the rate of successful characterization of gastroenteropancreatic neuroendocrine tumors (NETs) present with an increased somatostatin receptor, comparing CE-CT with CE-MRI, each in correlation with DOTATOC-PET. METHODS AND MATERIALS: 8 patients with GEP-NET were imaged using CE-MRI (Gd-EOB-DTPA), CE-CT (Imeron 400) and DOTATOC-PET. Contrast-enhancement of normal liver-tissue and metastasis was quantified with ROI-technique. Tumor delineation was assessed with visual-score in blind-read-analysis by two experienced radiologists. RESULTS: Out of 40 liver metastases in patients with NETs, all were detected by CE-MRI and the lesion extent could be adequately assessed, whereas CT failed to detect 20% of all metastases. The blind-read-score of CT in arterial and portal phase was median -0.65 and -1.4, respectively, and 2.7 for delayed-MRI. The quantitative ROI-analysis presented an improved contrast-enhancement-ratio with a median of 1.2, 1.6 and 3.3 for CE-CT arterial, portal-phase and delayed-MRI respectively. CONCLUSION: Late CE-MRI was superior to CE-CT in providing additionally morphologic characterization and exact lesion extension of hepatic metastases from neuroendocrine tumor detected with DOTATOC-PET. Therefore, late enhanced Gd-EOB-DTPA-MRI seems to be the adequate imaging modality for combination with DOTATOC-PET to provide complementary (macroscopic and molecular) tumor characterization in hepatic metastasized NETs.

Temporal resolution of dynamic angiography using flat panel volume CT: in vivo evaluation of time-dependent vascular pathologies.

BACKGROUND AND PURPOSE: Recently introduced fpVCT scanners can capture volumetric (4D) time-varying projections enabling whole-organ dynamic CTA imaging. The main objective of this study was to assess the temporal resolution of dynamic CTA in discriminating various phases of rapid and slow time-dependent neurovascular pathologies in animal models. MATERIALS AND METHODS: Animal models were created to assess phasic blood flow, subclavian steal phenomena, saccular aneurysms, and neuroperfusion under protocols approved by the SRAC. Animals with progressively increasing heart rate-Macaca sylvanus (~100 bpm), Oryctolagus cuniculus (NZW rabbit) (~150 bpm), Rattus norvegicus (~300 bpm), Mus musculus (~500 bpm)-were imaged to challenge the temporal resolution of the system. FpVCT, a research prototype with a 25 × 25 × 18 cm coverage, was used for dynamic imaging with the gantry rotation time varying from 3 to 5 seconds. Volumetric datasets with 50% temporal overlap were reconstructed; 4D datasets were analyzed by using the Leonardo workstation. RESULTS: Dynamic imaging by using fpVCT was capable of demonstrating the following phenomena: 1) subclavian steal in rabbits (ΔT ≅ 3-4 seconds); 2) arterial, parenchymal, and venous phases of blood flow in mice (ΔT ≅ 2 seconds), rabbits (ΔT ≅ 3-4 seconds), and Macaca sylvanus (ΔT ≅ 3-4 seconds); 3) sequential enhancement of the right and left side of the heart in Macaca sylvanus and white rabbits (ΔT ≅ 2 seconds); and 4) different times of the peak opacification of cervical and intracranial arteries, venous sinuses, and the jugular veins in these animals (smallest, ΔT ≅ 1.5-2 seconds). The perfusion imaging in all animals tested was limited due to the fast transit time through the brain and the low contrast resolution of fpVCT. CONCLUSIONS: Dynamic imaging by using fpVCT can distinguish temporal processes separated by >1.5 seconds. Neurovascular pathologies with a time constant >1.5 seconds can be evaluated noninvasively by using fpVCT.

3D printing based on imaging data: review of medical applications.

PURPOSE: Generation of graspable three-dimensional objects applied for surgical planning, prosthetics and related applications using 3D printing or rapid prototyping is summarized and evaluated. MATERIALS AND METHODS: Graspable 3D objects overcome the limitations of 3D visualizations which can only be displayed on flat screens. 3D objects can be produced based on CT or MRI volumetric medical images. Using dedicated post-processing algorithms, a spatial model can be extracted from image data sets and exported to machine-readable data. That spatial model data is utilized by special printers for generating the final rapid prototype model. RESULTS: Patient-clinician interaction, surgical training, medical research and education may require graspable 3D objects. The limitations of rapid prototyping include cost and complexity, as well as the need for specialized equipment and consumables such as photoresist resins. CONCLUSIONS: Medical application of rapid prototyping is feasible for specialized surgical planning and prosthetics applications and has significant potential for development of new medical applications.

Comparison of diagnostic quality and accuracy in color-coded versus gray-scale DCE-MR imaging display.

PURPOSE: The purpose of this study was to evaluate the diagnostic value and tumor-vascular display properties (microcirculation) of two different functional MRI post-processing and display (color and gray-scale display) techniques used in oncology. MATERIALS AND METHODS: The study protocol was approved by the IRB and written informed consent was obtained from all patients. 38 dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data sets of patients with malignant pleural-mesothelioma were acquired and post-processed. DCE-MRI was performed at 1.5 tesla with a T1-weighted 2D gradient-echo-sequence (TR 7.0 ms, TE 3.9 ms, 15 axial slices, 22 sequential repetitions), prior and during chemotherapy. Subtracting first image of contrast-enhanced-dynamic series from the last, produced gray-scale images. Color images were produced using a pharmacokinetic two-compartment model. Eight raters, blinded to diagnosis, by visual assessment of post-processed images evaluated both diagnostic quality of the images and vasculature of the tumor using a rating scale ranging from -5 to +5. The scores for vasculature were assessed by correlating with the maximum amplitude of the total-tumor-ROI for accuracy. RESULTS: Color coded images were rated as significantly higher in diagnostic quality and tumor vascular score than gray-scale images (p < 0.001, 0.005). ROI signal amplitude analysis and vascular ratings on color coded images were better correlated compared to gray-scale images rating (p < 0.05). CONCLUSION: Color coded images were shown to have higher diagnostic quality and accuracy with respect to tumor vasculature in DCE-MRI, therefore their implementation in clinical assessment and follow-up should be considered for wider application.

Image fusion using CT, MRI and PET for treatment planning, navigation and follow up in percutaneous RFA.

AIM: To evaluate the feasibility of fusion of morphologic and functional imaging modalities to facilitate treatment planning, probe placement, probe re-positioning, and early detection of residual disease following radiofrequency ablation (RFA) of cancer. METHODS: Multi-modality datasets were separately acquired that included functional (FDG-PET and DCE-MRI) and standard morphologic studies (CT and MRI). Different combinations of imaging modalities were registered and fused prior to, during, and following percutaneous image-guided tumor ablation with radiofrequency. Different algorithms and visualization tools were evaluated for both intra-modality and inter-modality image registration using the software MIPAV (Medical Image Processing, Analysis and Visualization). Semi-automated and automated registration algorithms were used on a standard PC workstation: 1) landmark-based least-squares rigid registration, 2) landmark-based thin-plate spline elastic registration, and 3) automatic voxel-similarity, affine registration. RESULTS: Intra- and inter-modality image fusion were successfully performed prior to, during and after RFA procedures. Fusion of morphologic and functional images provided a useful view of the spatial relationship of lesion structure and functional significance. Fused axial images and segmented three-dimensional surface models were used for treatment planning and post-RFA evaluation, to assess potential for optimizing needle placement during procedures. CONCLUSION: Fusion of morphologic and functional images is feasible before, during and after radiofrequency ablation of tumors in abdominal organs. For routine use, the semi-automated registration algorithms may be most practical. Image fusion may facilitate interventional procedures like RFA and should be further evaluated.