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Frontiers in Oncology 2014Radioembolization (RE) of liver cancer with (90)Y-microspheres has been applied in the last two decades with notable responses and acceptable toxicity. Two types of... (Review)
Review
Radioembolization (RE) of liver cancer with (90)Y-microspheres has been applied in the last two decades with notable responses and acceptable toxicity. Two types of microspheres are available, glass and resin, the main difference being the activity/sphere. Generally, administered activities are established by empirical methods and differ for the two types. Treatment planning based on dosimetry is a prerogative of few centers, but has notably gained interest, with evidence of predictive power of dosimetry on toxicity, lesion response, and overall survival (OS). Radiobiological correlations between absorbed doses and toxicity to organs at risk, and tumor response, have been obtained in many clinical studies. Dosimetry methods have evolved from the macroscopic approach at the organ level to voxel analysis, providing absorbed dose spatial distributions and dose-volume histograms (DVH). The well-known effects of the external beam radiation therapy (EBRT), such as the volume effect, underlying disease influence, cumulative damage in parallel organs, and different tolerability of re-treatment, have been observed also in RE, identifying in EBRT a foremost reference to compare with. The radiobiological models - normal tissue complication probability and tumor control probability - and/or the style (DVH concepts) used in EBRT are introduced in RE. Moreover, attention has been paid to the intrinsic different activity distribution of resin and glass spheres at the microscopic scale, with dosimetric and radiobiological consequences. Dedicated studies and mathematical models have developed this issue and explain some clinical evidences, e.g., the shift of dose to higher toxicity thresholds using glass as compared to resin spheres. This paper offers a comprehensive review of the literature incident to dosimetry and radiobiological issues in RE, with the aim to summarize the results and to identify the most useful methods and information that should accompany future studies.
PubMed: 25191640
DOI: 10.3389/fonc.2014.00210 -
Clinical & Translational Immunology 2023The leading cause of mortality in patients with rheumatoid arthritis is atherosclerotic cardiovascular disease (CVD). We have shown that murine arthritis impairs...
OBJECTIVES
The leading cause of mortality in patients with rheumatoid arthritis is atherosclerotic cardiovascular disease (CVD). We have shown that murine arthritis impairs atherosclerotic lesion regression, because of cellular cholesterol efflux defects in haematopoietic stem and progenitor cells (HSPCs), causing monocytosis and impaired atherosclerotic regression. Therefore, we hypothesised that improving cholesterol efflux using a Liver X Receptor (LXR) agonist would improve cholesterol efflux and improve atherosclerotic lesion regression in arthritis.
METHODS
mice were fed a western-type diet for 14 weeks to initiate atherogenesis, then switched to a chow diet to induce lesion regression and divided into three groups; (1) control, (2) K/BxN serum transfer inflammatory arthritis (K/BxN) or (3) K/BxN arthritis and LXR agonist T0901317 daily for 2 weeks.
RESULTS
LXR activation during murine inflammatory arthritis completely restored atherosclerotic lesion regression in arthritic mice, evidenced by reduced lesion size, macrophage abundance and lipid content. Mechanistically, serum from arthritic mice promoted foam cell formation, demonstrated by increased cellular lipid accumulation in macrophages and paralleled by a reduction in mRNA of the cholesterol efflux transporters , and . T0901317 reduced lipid loading and increased and expression in macrophages exposed to arthritic serum and increased ABCA1 levels in atherosclerotic lesions of arthritic mice. Moreover, arthritic clinical score was also attenuated with T0901317.
CONCLUSION
Taken together, we show that the LXR agonist T0901317 rescues impaired atherosclerotic lesion regression in murine arthritis because of enhanced cholesterol efflux transporter expression and reduced foam cell development in atherosclerotic lesions.
PubMed: 37091327
DOI: 10.1002/cti2.1446 -
Medical Physics Aug 2022A common rule of thumb for object detection is the Rose criterion, which states that a signal must be five standard deviations above background to be detectable to a...
BACKGROUND
A common rule of thumb for object detection is the Rose criterion, which states that a signal must be five standard deviations above background to be detectable to a human observer. The validity of the Rose criterion in CT imaging is limited due to the presence of correlated noise. Recent reconstruction and denoising methodologies are also able to restore apparent image quality in very noisy conditions, and the ultimate limits of these methodologies are not yet known.
PURPOSE
To establish a lower bound on the minimum achievable signal-to-noise ratio (SNR) for object detection, below which detection performance is poor regardless of reconstruction or denoising methodology.
METHODS
We consider a numerical observer that operates on projection data and has perfect knowledge of the background and the objects to be detected, and determine the minimum projection SNR that is necessary to achieve predetermined lesion-level sensitivity and case-level specificity targets. We define a set of discrete signal objects that encompasses any lesion of interest and could include lesions of different sizes, shapes, and locations. The task is to determine which object of is present, or to state the null hypothesis that no object is present. We constrain each object in to have equivalent projection SNR and use Monte Carlo methods to calculate the required projection SNR necessary. Because our calculations are performed in projection space, they impose an upper limit on the performance possible from reconstructed images. We chose to be a collection of elliptical or circular low contrast metastases and simulated detection of these objects in a parallel beam system with Gaussian statistics. Unless otherwise stated, we assume a target of 80% lesion-level sensitivity and 80% case-level specificity and a search field of view that is 6 cm by 6 cm by 10 slices.
RESULTS
When contains only a single object, our problem is equivalent to two-alternative forced choice (2AFC) and the required projection SNR is 1.7. When consists of circular 6-mm lesions at different locations in space, the required projection SNR is 5.1. When is extended to include ellipses and circles of different sizes, the required projection SNR increases to 5.3. The required SNR increases if the sensitivity target, specificity target, or search field of view increases.
CONCLUSIONS
Even with perfect knowledge of the background and target objects, the ideal observer still requires an SNR of approximately 5. This is a lower bound on the SNR that would be required in real conditions, where the background and target objects are not known perfectly. Algorithms that denoise lesions with less than 5 projection SNR, regardless of the denoising methodology, are expected to show vanishing effects or false positive lesions.
Topics: Algorithms; Humans; Image Processing, Computer-Assisted; Monte Carlo Method; Phantoms, Imaging; Radiation Dosage; Signal-To-Noise Ratio; Tomography, X-Ray Computed
PubMed: 35754205
DOI: 10.1002/mp.15832 -
NeuroImage Aug 2021White matter lesions are a very common finding on MRI in older adults and their presence increases the risk of stroke and dementia. Accurate and computationally... (Comparative Study)
Comparative Study
OBJECTIVES
White matter lesions are a very common finding on MRI in older adults and their presence increases the risk of stroke and dementia. Accurate and computationally efficient modelling methods are necessary to map the association of lesion incidence with risk factors, such as hypertension. However, there is no consensus in the brain mapping literature whether a voxel-wise modelling approach is better for binary lesion data than a more computationally intensive spatial modelling approach that accounts for voxel dependence.
METHODS
We review three regression approaches for modelling binary lesion masks including mass-univariate probit regression modelling with either maximum likelihood estimates, or mean bias-reduced estimates, and spatial Bayesian modelling, where the regression coefficients have a conditional autoregressive model prior to account for local spatial dependence. We design a novel simulation framework of artificial lesion maps to compare the three alternative lesion mapping methods. The age effect on lesion probability estimated from a reference data set (13,680 individuals from the UK Biobank) is used to simulate a realistic voxel-wise distribution of lesions across age. To mimic the real features of lesion masks, we propose matching brain lesion summaries (total lesion volume, average lesion size and lesion count) across the reference data set and the simulated data sets. Thus, we allow for a fair comparison between the modelling approaches, under a realistic simulation setting.
RESULTS
Our findings suggest that bias-reduced estimates for voxel-wise binary-response generalized linear models (GLMs) overcome the drawbacks of infinite and biased maximum likelihood estimates and scale well for large data sets because voxel-wise estimation can be performed in parallel across voxels. Contrary to the assumption of spatial dependence being key in lesion mapping, our results show that voxel-wise bias-reduction and spatial modelling result in largely similar estimates.
CONCLUSIONS
Bias-reduced estimates for voxel-wise GLMs are not only accurate but also computationally efficient, which will become increasingly important as more biobank-scale neuroimaging data sets become available.
Topics: Computer Simulation; Humans; Image Processing, Computer-Assisted; Models, Theoretical; Neuroimaging; White Matter
PubMed: 33895308
DOI: 10.1016/j.neuroimage.2021.118090 -
Philosophical Transactions of the Royal... 2014The cognitive analysis of adult language disorders continues to draw heavily on linguistic theory, but increasingly it reflects the influence of connectionist, spreading... (Review)
Review
The cognitive analysis of adult language disorders continues to draw heavily on linguistic theory, but increasingly it reflects the influence of connectionist, spreading activation models of cognition. In the area of spoken word production, 'localist' connectionist models represent a natural evolution from the psycholingistic theories of earlier decades. By contrast, the parallel distributed processing framework forces more radical rethinking of aphasic impairments. This paper exemplifies these multiple influences in contemporary cognitive aphasiology. Topics include (i) what aphasia reveals about semantic-phonological interaction in lexical access; (ii) controversies surrounding the interpretation of semantic errors and (iii) a computational account of the relationship between naming and word repetition in aphasia. Several of these topics have been addressed using case series methods, including computational simulation of the individual, quantitative error patterns of diverse groups of patients and analysis of brain lesions that correlate with error rates and patterns. Efforts to map the lesion correlates of nonword errors in naming and repetition highlight the involvement of sensorimotor areas in the brain and suggest the need to better integrate models of word production with models of speech and action.
Topics: Adult; Aphasia; Articulation Disorders; Brain Mapping; Cognition; Humans; Mental Recall; Models, Psychological; Neuroimaging; Repetition Priming; Semantics
PubMed: 24324234
DOI: 10.1098/rstb.2012.0390 -
Journal of Cardiovascular... Apr 2022Ablation of papillary muscles (PMs) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect...
INTRODUCTION
Ablation of papillary muscles (PMs) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect optimal radiofrequency (RF) delivery. Yet, no previous study investigated the association between catheter orientation and PM lesion size. We evaluated ablation lesion characteristics with various catheter orientations relative to the PM tissue during open irrigated ablation, using a standardized, experimental setting.
METHODS
Viable bovine PM was positioned on a load cell in a circulating saline bath. RF ablation was performed over PM tissue at 50 W, with the open irrigated catheter positioned either perpendicular or parallel to the PM surface. Applied force was 10 g. Ablation lesions were sectioned and underwent quantitative morphometric analysis.
RESULTS
A catheter position oriented directly perpendicular to the PM tissue resulted in the largest ablation lesion volumes and depths compared with ablation with the catheter parallel to PM tissue (75.26 ± 8.40 mm vs. 34.04 ± 2.91 mm , p < .001) and (3.33 ± 0.18 mm vs. 2.24 ± 0.10 mm, p < .001), respectively. There were no significant differences in initial impedance, peak voltage, peak current, or overall decrease in impedance among groups. Parallel catheter orientation resulted in higher peak temperature (41.33 ± 0.28°C vs. 40.28 ± 0.24°C, p = .003), yet, there were no steam pops in either group.
CONCLUSION
For PM ablation, catheter orientation perpendicular to the PM tissue achieves more effective and larger ablation lesions, with greater lesion depth. This may have implications for the chosen ventricular access approach, the type of catheter used, consideration for remote navigation, and steerable sheaths.
Topics: Animals; Catheter Ablation; Catheters; Cattle; Heart Ventricles; Papillary Muscles; Therapeutic Irrigation
PubMed: 35133050
DOI: 10.1111/jce.15408 -
Dermatopathology (Basel, Switzerland) Aug 2022Acral melanocytic neoplasms, including acral melanocytic nevus and acral melanoma, are common melanocytic lesions in Asian populations. Both lesions occur on the volar... (Review)
Review
Acral melanocytic neoplasms, including acral melanocytic nevus and acral melanoma, are common melanocytic lesions in Asian populations. Both lesions occur on the volar surface of the hands and feet, and on nail units. Acral melanocytic nevi occur on the arch area of the sole, whereas acral melanomas frequently occur on weight-bearing areas of the sole, and on the fingernails. Therefore, the development of acral melanoma may be associated with chronic pressure, physical stress, or trauma. Dermoscopy is a useful adjunctive diagnostic tool for differential diagnosis. Acral melanocytic nevus is characterized by a parallel furrow pattern, whereas acral melanoma has a parallel ridge pattern. Genetic alterations are also different between the two types of lesion. and mutations are common in acral melanocytic nevus, whereas acral melanoma shows lower rates of , , , and mutations and remarkable copy number variations in genes such as , , , , and . Sentinel lymph node biopsy is important for staging and prognosis. Contemporary treatments for melanoma include targeted therapy for mutations and immunotherapy, such as anti-PD1 inhibitors.
PubMed: 35997352
DOI: 10.3390/dermatopathology9030035 -
Frontiers in Neurology 2021The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and... (Review)
Review
The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.
PubMed: 33981281
DOI: 10.3389/fneur.2021.561458 -
Journal of Experimental & Clinical... Jun 2023Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60-70% of...
BACKGROUND
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60-70% of event-free survival for localized disease at diagnosis. However, for metastatic disease, the prognosis is dismal. Exploiting immune system activation in the setting of such unfavorable mesenchymal tumors represents a new therapeutic challenge.
METHODS
In immune competent OS mouse models bearing two contralateral lesions, we tested the efficacy of intralesional administration of a TLR9 agonist against the treated and not treated contralateral lesion evaluating abscopal effect. Multiparametric flow cytometry was used to evaluate changes of the tumor immune microenviroment. Experiments in immune-deficient mice allowed the investigation of the role of adaptive T cells in TLR9 agonist effects, while T cell receptor sequencing was used to assess the expansion of specific T cell clones.
RESULTS
TLR9 agonist strongly impaired the growth of locally-treated tumors and its therapeutic effect also extended to the contralateral, untreated lesion. Multiparametric flow cytometry showed conspicuous changes in the immune landscape of the OS immune microenvironment upon TLR9 engagement, involving a reduction in M2-like macrophages, paralleled by increased infiltration of dendritic cells and activated CD8 T cells in both lesions. Remarkably, CD8 T cells were needed for the induction of the abscopal effect, whereas they were not strictly necessary for halting the growth of the treated lesion. T cell receptor (TCR) sequencing of tumor infiltrating CD8 T cells showed the expansion of specific TCR clones in the treated tumors and, remarkably, their selected representation in the contralateral untreated lesions, providing the first evidence of the rewiring of tumor-associated T cell clonal architectures.
CONCLUSIONS
Overall these data indicate that the TLR9 agonist acts as an in situ anti-tumor vaccine, activating an innate immune response sufficient to suppress local tumor growth while inducing a systemic adaptive immunity with selective expansion of CD8 T cell clones, which are needed for the abscopal effect.
Topics: Animals; Mice; Toll-Like Receptor 9; CD8-Positive T-Lymphocytes; Adaptive Immunity; Osteosarcoma; Bone Neoplasms; Tumor Microenvironment
PubMed: 37365634
DOI: 10.1186/s13046-023-02731-z -
Heliyon Dec 2023A supervised deep learning network like the UNet has performed well in segmenting brain anomalies such as lesions and tumours. However, such methods were proposed to...
A supervised deep learning network like the UNet has performed well in segmenting brain anomalies such as lesions and tumours. However, such methods were proposed to perform on single-modality or multi-modality images. We use the Hybrid UNet Transformer (HUT) to improve performance in single-modality lesion segmentation and multi-modality brain tumour segmentation. The HUT consists of two pipelines running in parallel, one of which is UNet-based and the other is Transformer-based. The Transformer-based pipeline relies on feature maps in the intermediate layers of the UNet decoder during training. The HUT network takes in the available modalities of 3D brain volumes and embeds the brain volumes into voxel patches. The transformers in the system improve global attention and long-range correlation between the voxel patches. In addition, we introduce a self-supervised training approach in the HUT framework to enhance the overall segmentation performance. We demonstrate that HUT performs better than the state-of-the-art network SPiN in the single-modality segmentation on Anatomical Tracings of Lesions After Stroke (ATLAS) dataset by 4.84% of Dice score and a significant 41% in the Hausdorff Distance score. HUT also performed well on brain scans in the Brain Tumour Segmentation (BraTS20) dataset and demonstrated an improvement over the state-of-the-art network nnUnet by 0.96% in the Dice score and 4.1% in the Hausdorff Distance score.
PubMed: 38046150
DOI: 10.1016/j.heliyon.2023.e22412