Radiomics modelling in rectal cancer to predict disease-free survival: evaluation of different approaches.

BACKGROUND: Radiomics may be useful in rectal cancer management. The aim of this study was to assess and compare different radiomics approaches over qualitative evaluation to predict disease-free survival (DFS) in patients with locally advanced rectal cancer treated with neoadjuvant therapy. METHODS: Patients from a phase II, multicentre, randomized study (GRECCAR4; NCT01333709) were included retrospectively as a training set. An independent cohort of patients comprised the independent test set. For both time points and both sets, radiomic features were extracted from two-dimensional manual segmentation (MS), three-dimensional (3D) MS, and from bounding boxes. Radiomics predictive models of DFS were built using a hyperparameters-tuned random forests classifier. Additionally, radiomics models were compared with qualitative parameters, including sphincter invasion, extramural vascular invasion as determined by MRI (mrEMVI) at baseline, and tumour regression grade evaluated by MRI (mrTRG) after chemoradiotherapy (CRT). RESULTS: In the training cohort of 98 patients, all three models showed good performance with mean(s.d.) area under the curve (AUC) values ranging from 0.77(0.09) to 0.89(0.09) for prediction of DFS. The 3D radiomics model outperformed qualitative analysis based on mrEMVI and sphincter invasion at baseline (P = 0.038 and P = 0.027 respectively), and mrTRG after CRT (P = 0.017). In the independent test cohort of 48 patients, at baseline and after CRT the AUC ranged from 0.67(0.09) to 0.76(0.06). All three models showed no difference compared with qualitative analysis in the independent set. CONCLUSION: Radiomics models can predict DFS in patients with locally advanced rectal cancer.

Advanced dual-energy CT applications for the evaluation of the soft tissues of the neck.

There are multiple emerging advanced computed tomography (CT) applications for the evaluation of the neck, many based on dual-energy CT (DECT). DECT is an advanced form of CT in which scan acquisition is performed at two different energies, enabling spectral tissue characterisation beyond what is possible with conventional single-energy CT and potentially providing a new horizon for quantitative analysis and tissue characterisation, particularly in oncological imaging. The purpose of this review is to familiarise the reader with DECT principles and review different clinical applications for the evaluation of the soft tissues of the neck. The article will begin with an overview of DECT scan acquisition, material characterisation, reconstructions, and basic considerations for implementation in the clinical setting. This will then be followed by a review of different clinical applications. The focus will be on oncological imaging, but artefact reduction and other miscellaneous applications will also be discussed.

Optimal Virtual Monochromatic Images for Evaluation of Normal Tissues and Head and Neck Cancer Using Dual-Energy CT.

BACKGROUND AND PURPOSE: Dual-energy CT is not used routinely for evaluation of the head and neck, and there is no consensus on the optimal virtual monochromatic image energies for evaluating normal tissues or head and neck cancer. We performed a quantitative evaluation to determine the optimal virtual monochromatic images for visualization of normal tissues, head and neck squamous cell carcinoma, and lymphadenopathy. MATERIALS AND METHODS: Dual-energy CT scans from 10 healthy patients and 30 patients with squamous cell carcinoma were evaluated at different virtual monochromatic energy levels ranging from 40 to 140 keV. The signal-to-noise ratios of muscles at 6 different levels, glands (parotid, sublingual, submandibular, and thyroid), 30 tumors, and 17 metastatic lymph nodes were determined as measures of optimal image quality. Lesion attenuation and contrast-to-noise ratios (compared with those of muscle) were evaluated to assess lesion conspicuity. RESULTS: The optimal signal-to-noise ratio for all the tissues was at 65 keV (P < .0001). However, tumor attenuation (P < .0001), attenuation difference between tumor and muscles (P = .03), and lesion contrast-to-noise ratios (P < .0001) were highest at 40 keV. CONCLUSIONS: The optimal image signal-to-noise ratio is at 65 keV, but tumor conspicuity compared with that of muscle is greatest at 40 keV. Optimal evaluation of the neck may be best achieved by a multiparametric approach, with 65-keV virtual monochromatic images providing the best overall image quality and targeted use of 40-keV virtual monochromatic images for tumor evaluation.

Different spectral hounsfield unit curve and high-energy virtual monochromatic image characteristics of squamous cell carcinoma compared with nonossified thyroid cartilage.

BACKGROUND AND PURPOSE: The attenuation of normal nonossified thyroid cartilage can be similar to that of head and neck squamous cell carcinoma on CT. We compared dual-energy CT spectral Hounsfield unit attenuation characteristics of nonossified thyroid cartilage with that of squamous cell carcinoma to determine the optimal virtual monochromatic image reconstruction energy levels for distinguishing tumor from normal nonossified thyroid cartilage. MATERIALS AND METHODS: Dual-energy CT scans from 30 patients with histopathology-proved squamous cell carcinoma at different primary sites (laryngeal and nonlaryngeal) and 10 healthy patients were evaluated. Patients were scanned with a 64-section single-source scanner with fast-kilovolt (peak) switching, and scans were reconstructed at different virtual monochromatic energy levels ranging from 40 to 140 keV. Spectral attenuation curves of tumor and nonossified thyroid cartilage were quantitatively evaluated and compared. Any part of the tumor invading the cartilage, when present, was excluded from ROI analysis to avoid cross-contamination from areas where there could be a mixture of cartilage and invading tumor. RESULTS: Normal nonossified thyroid cartilage had a characteristic, predictable spectral attenuation curve that was different from that of tumors. The greatest difference in attenuation of nonossified cartilage compared with tumor was on virtual monochromatic images of ≥95 keV (P < .0001), with sharp contrast between the relatively high attenuation of nonossified cartilage compared with that of tumor. CONCLUSIONS: Head and neck squamous cell carcinoma has significantly different attenuation on virtual monochromatic images of ≥95 keV, compared with nonossified thyroid cartilage.

The next level of radiology peer review: enterprise-wide education and improvement.

It is essential to the future of radiology that our profession own and embrace the objectives and methodology of peer review. The authors describe a natural evolution of peer review away from measurement and error identification toward the goal of performance improvement for the entire profession by allowing everyone to learn from the mistakes of everyone else. This can be accomplished by a comprehensive program of reviewer education, cross-platform anonymous prospective data collection, third-party expert arbitration, and meaningful sharing of results with the entire body of radiologists and residency programs. Such a system would require robust informatics and leadership from provincial and state as well as national radiologist associations. In so doing, apprehension and risk for the individual radiologist could be minimized, while ensuring that everyone benefits from others' mistakes, thereby measurably reducing errors across the entire enterprise. Seldom, and only in cases of significant and immediate patient risk, would an individual's identity and performance ever need to be made visible, even to the administrators of the program.

Diagnosis and temporal evolution of signs of intracranial hypotension on MRI of the brain.

INTRODUCTION: A comprehensive evaluation of cranial magnetic resonance imagings (MRIs) of 23 patients with intracranial hypotension (IH) was performed, and the evolution of the abnormalities on follow-up MRIs was correlated with the clinical outcome. MATERIALS AND METHODS: The MRI report database at the University Health Network in Toronto was searched, and 23 cases of IH were identified between 2001 and 2007. A retrospective review of the MRIs of the brain and the electronic patient chart was performed. A control group of 40 subjects was also selected to complement the analysis of the pituitary gland. RESULTS: A positive venous distention sign (VDS) was observed in 23 out of 23 patients and was the first sign to disappear on early follow-up scans following successful treatment. Pachymeningeal enhancement was seen in 23 out of 23 patients, and pachymeningeal thickening was detectable on unenhanced fluid attenuation inversion recovery (FLAIR) sequences in 17 out of 23 patients (74%). An increase in pituitary size in IH was also demonstrated based on the measured pituitary height and was qualitatively detectable in 12 out of 21 (57%) patients as the protrusion of the pituitary gland above the sella turica (two postpartum patients were excluded from this analysis). Overall, there was good correlation between the imaging findings and clinical outcome following treatment. CONCLUSION: Accurate diagnosis and follow-up of IH should be possible is some patients on unenhanced MRI of the brain by combining the signs on FLAIR and sagittal T1W images, enabling timely diagnosis in unsuspected cases and avoiding unnecessary administration of gadolinium compounds. In addition, VDS might be useful for early assessment of response to treatment.

The venous distension sign: a diagnostic sign of intracranial hypotension at MR imaging of the brain.

BACKGROUND AND PURPOSE: Patients with intracranial hypotension (IH) demonstrate intracranial venous enlargement with a characteristic change in contour of the transverse sinus seen on routine T1-weighted sagittal imaging. In IH, the inferior margin of the midportion of the dominant transverse sinus acquires a distended convex appearance; we have termed this the venous distension sign (VDS). This is distinct from the normal appearance of this segment, which usually has a slightly concave or straight lower margin. This sign is introduced, and its performance as a test for the presence of this disease is evaluated. MATERIALS AND METHODS: The transverse sinuses on T1-weighted sagittal imaging of 15 patients with IH and 15 control patients were independently assessed in a blinded fashion by 3 readers for the presence of a VDS. A present or absent VDS was determined for each patient by each reader, and a consensus result for each patient was determined by unanimity or majority rule. RESULTS: Using the VDS, the readers correctly identified 93% (14 of 15) of the IH patients and similarly 93% (14 of 15) of the control patients. There was a high rate of agreement among the readers for the interpretation of the VDS (multirater kappa = 0.82). The overall sensitivity of the VDS for the diagnosis of intracranial hypotension was 94%. Specificity was also 94%. CONCLUSION: The VDS appears to be an accurate test for the presence or absence of IH and may be helpful in the evaluation of these patients.

A distal upstream enhancer from the myelin basic protein gene regulates expression in myelin-forming schwann cells.

In peripheral nerves, large caliber axons are ensheathed by myelin-elaborating Schwann cells. Multiple lines of evidence demonstrate that expression of the genes encoding myelin structural proteins occurs in Schwann cells in response to axonal instructions. To gain further insight into the mechanisms controlling myelin gene expression, we used reporter constructs in transgenic mice to search for the DNA elements that regulate the myelin basic protein (MBP) gene. Through this in vivo investigation, we provide evidence for the participation of multiple, widely distributed, positive and negative elements in the overall control of MBP expression. Notably, all constructs bearing a 0.6 kb far-upstream sequence, designated Schwann cell enhancer 1 (SCE1), expressed at high levels in myelin-forming Schwann cells. In addition, robust targeting activity conferred by SCE1 was shown to be independent of other MBP 5' flanking sequence. These observations suggest that SCE1 will make available a powerful tool to drive transgene expression in myelinating Schwann cells and that a focused analysis of the SCE1 sequence will lead to the identification of transcription factor binding sites that positively regulate MBP expression.

Preparation of nuclear extracts from myelinating Schwann cells.

Myelination of peripheral nerve fibres is performed by Schwann cells and is associated with the coordinate upregulation of lipid synthesis and multiple genes encoding myelin-specific proteins. Both the decision to enter into a myelinating phenotype and subsequently, the quantity of myelin that each Schwann cell elaborates appear to be controlled by axonal signals. Understanding of the relevant signaling pathways and the downstream transcription factors and cis elements that confer myelin gene expression is notably limited. In large part, this has resulted directly from a lack of methods for obtaining nuclear extracts from myelinating Schwann cells thus precluding the application of numerous powerful molecular techniques. In this report, we describe a method that overcomes this limitation for the myelinating Schwann cells in the sciatic nerves of the mouse. During the evolution of the method, its effectiveness was monitored using an oligonucleotide containing the binding site for KROX-20, a transcription factor known to be present in myelinating Schwann cells. Following technical development, the optimized protocol has proven to be entirely reliable and thus novel experimental strategies now can be applied to the investigation of the molecular mechanisms controlling gene expression in peripheral nerves.

In rat hippocampal slices, NMDA receptor-mediated EPSPs are more sensitive to hypoxia than AMPA receptor-mediated EPSPs.

In slices kept at 33 degrees C, N-methyl-D-aspartate (NMDA) receptor- and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated field excitatory post-synaptic potentials (EPSPs) were pharmacologically isolated in CA1. Both types of EPSPs were reversibly blocked by 3 min of hypoxia (95% N2/5% CO2); but NMDA receptor-mediated EPSPs were consistently blocked earlier and recovered later than AMPA receptor-mediated EPSPs, recorded in the same slice. This difference may be due to inactivation of NMDA receptors by hypoxia-induced acidity and/or rise in internal [Ca2+].

Econazole, a blocker of Ca2+ influx, selectively suppresses LTP of EPSPs in hippocampal slices.

Econazole--an agent that suppresses Ca2+ influx triggered by depletion of internal Ca-stores in non-excitable cells--was bath-applied to submerged slices from Sprague-Dawley rats. Econazole (15-20 microM) had no consistent effect on afferent volleys, EPSPs or population spikes; but in seven out of nine slices, it prevented the induction of tetanic long-term potentiation (LTP) of field EPSPS. By contrast, all slices showed a marked LTP of population spikes. Ca2+ influx induced by tetanic depletion of Ca2+ stores may be essential for LTP of excitatory synaptic transmission.

Adenosine antagonists have differential effects on induction of long-term potentiation in hippocampal slices.

How adenosine leakage and tetanic release might affect long-term potentiation (LTP) was investigated by applying adenosine antagonists 8(p-sulfophenyl)theophylline (8SPT) or 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. In the presence of 8SPT--at concentrations (10-50 microM) which block both A1 and A2 receptors--the same tetani consistently evoked LTP of population spikes but not of excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A1 receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A1 receptors but on the other facilitates LTP via A2 receptors. In a second set of experiments, 8SPT (50-100 microM) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A2 receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP induction.

A bacterial toxicity assay performed with microplates, microluminometry and Microtox reagent.

We have developed a procedure for undertaking a Microtox-based test by coupling microplate and microluminometric technologies. Sample dilutions are prepared in a 96-well polystyrene microplate kept at 15 degrees C, while the Microtox reagent and diluent are placed in an opaque, microluminometry-compatible 96-well microplate also kept at 15 degrees C. Exposure begins when sample aliquots are brought into contact with bacterial reagents in the opaque microplate. After specific exposure times (5, 15, 30 and 60 min), bacterial luminescence is rapidly measured by placing the opaque microplate in a microluminometer. Reproducibility of the procedure, as well as general agreement of EC50 end-point values with published reports, is demonstrated herein after toxicity trials with six metals (Ni2+, Cd2+, Zn2+, Pb2+, Cu2+ and Cr6+). Results suggest that a 60-min exposure time may have value in getting more "sensitivity mileage" out of this Microtox-based assay. This microplate procedure possesses attractive features that augment sample throughput and information output. Further refinement and validation studies are ongoing in our laboratories.