Diffusion-weighted MRI for detecting prostate tumour in men at increased genetic risk.

Background: Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk.

Methods: 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.

In Vivo response to compression of 35 breast lesions observed with a two-dimensional locally regularized strain estimation method.

The objective of this study was to assess the in vivo performance of our 2-D locally regularized strain estimation method with 35 breast lesions, mainly cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as well as the method's adaptability, led to an algorithm that is able to track tissue motion from radiofrequency ultrasound images acquired in clinical conditions. Particular attention was paid to strain estimation reliability, implying analysis of the mean normalized correlation coefficient maps.

Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement.

Purpose: To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion.

Methods: Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b = 100, 500, 800 s/mm(2)) during free-breathing. Regions of interest around target lesions on computed b = 800 s/mm(2) images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model).

Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.

Purpose: The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy.

Procedures: Z spectra of solutions of the CPG2 substrate, 3,5-difluorobenzoyl-L-glutamate (amide), and glutamate (amine) were acquired at 11.7 T, 37 °C, across different pH (5-8).

Fatigue during chemoradiotherapy for nasopharyngeal cancer and its relationship to radiation dose distribution in the brain.

Background And Purpose: Fatigue during head and neck radiotherapy may be related to radiation dose to the central nervous system (CNS). The impact of patient, tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal cancer patients undergoing chemoradiotherapy.

Material And Methods: Radiation dose to the following retrospectively-delineated CNS structures; brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia (BG) and clinical variables were related to incidence of ⩾ grade 2 fatigue in 40 patients.

Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique.

Background: Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its sensitivity/specificity, document tumour-to-stromal contrast and establish the effect of imaging on surgical management.

Evaluation and immunohistochemical qualification of carbogen-induced ΔR₂ as a noninvasive imaging biomarker of improved tumor oxygenation.

Purpose: To evaluate and histologically qualify carbogen-induced ΔR2 as a noninvasive magnetic resonance imaging biomarker of improved tumor oxygenation using a double 2-nitroimidazole hypoxia marker approach.

Methods And Materials: Multigradient echo images were acquired from mice bearing GH3 prolactinomas, preadministered with the hypoxia marker CCI-103F, to quantify tumor R2 during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O2, 5% CO2), during which a second hypoxia marker, pimonidazole, was administered via an intraperitoneal line, and an additional set of identical multigradient echo images acquired to quantify any changes in tumor R2.

¹H NMR and hyperpolarized ¹³C NMR assays of pyruvate-lactate: a comparative study.

Pyruvate-lactate exchange is mediated by the enzyme lactate dehydrogenase (LDH) and is central to the altered energy metabolism in cancer cells. The measurement of exchange kinetics using hyperpolarized (13) C NMR has provided a biomarker of response to novel therapeutics. However, the observable signal is restricted to the exchanging hyperpolarized (13) C pools and the endogenous pools of (12) C-labelled metabolites are invisible in these measurements.

Clutter elimination for deep clinical optoacoustic imaging using localised vibration tagging (LOVIT).

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology.

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this.

Optical photon transport in powdered-phosphor scintillators. Part II. Calculation of single-scattering transport parameters.

Purpose: Monte Carlo methods based on the Boltzmann transport equation (BTE) have previously been used to model light transport in powdered-phosphor scintillator screens. Physically motivated guesses or, alternatively, the complexities of Mie theory have been used by some authors to provide the necessary inputs of transport parameters. The purpose of Part II of this work is to: (i) validate predictions of modulation transform function (MTF) using the BTE and calculated values of transport parameters, against experimental data published for two Gd2O2S:Tb screens; (ii) investigate the impact of size-distribution and emission spectrum on Mie predictions of transport parameters; (iii) suggest simpler and novel geometrical optics-based models for these parameters and compare to the predictions of Mie theory.

Optical photon transport in powdered-phosphor scintillators. Part 1. Multiple-scattering and validity of the Boltzmann transport equation.

Purpose: In Part 1 of this two-part work, predictions for light transport in powdered-phosphor screens are made, based on three distinct approaches. Predictions of geometrical optics-based ray tracing through an explicit microscopic model (EMM) for screen structure are compared to a Monte Carlo program based on the Boltzmann transport equation (BTE) and Swank's diffusion equation solution. The purpose is to: (I) highlight the additional assumptions of the BTE Monte Carlo method and Swank's model (both previously used in the literature) with respect to the EMM approach; (II) demonstrate the equivalences of the approaches under well-defined conditions and; (III) identify the onset and severity of any discrepancies between the models.

BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients.

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

Objective: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics.

Subjects And Methods: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil.

New MR techniques in gynecologic cancer.

Objective: Functional MR techniques report on a variety of biologic features of tumors: dynamic contrast-enhanced, diffusion-weighted, and intrinsic susceptibility-weighted MRI and MR spectroscopy reflect, at a simplistic level, vascularity, cellularity, hypoxic status, and metabolism, respectively. This article reviews the evidence for each of the functional MR readouts to determine these clinical end points and thus influence the management of ovarian, endometrial, and cervical cancer.

Conclusion: These techniques may be implemented in gynecologic malignancies to detect, characterize, and stage tumors as well as potentially to predict the outcome and measure response to treatment.

Novel strategies to test biological hypotheses in early drug development for advanced prostate cancer.

Background: Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic.

Content: We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs.

Summary: With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated.

Evaluation of clinically translatable MR imaging biomarkers of therapeutic response in the TH-MYCN transgenic mouse model of neuroblastoma.

Purpose: To evaluate noninvasive and clinically translatable magnetic resonance (MR) imaging biomarkers of therapeutic response in the TH-MYCN transgenic mouse model of aggressive, MYCN-amplified neuroblastoma.

Materials And Methods: All experiments were performed in accordance with the local ethical review panel and the UK Home Office Animals Scientific Procedures Act 1986 and with the UK National Cancer Research Institute guidelines for the welfare of animals in cancer research. Multiparametric MR imaging was performed of abdominal tumors found in the TH-MYCN model.

Deformation-compensated averaging for clutter reduction in epiphotoacoustic imaging in vivo.

Photoacoustic imaging, based on ultrasound detected after laser irradiation, is an extension to diagnostic ultrasound for imaging the vasculature, blood oxygenation and the uptake of optical contrast media with promise for cancer diagnosis. For versatile scanning, the irradiation optics is preferably combined with the acoustic probe in an epi-style arrangement avoiding acoustically dense tissue in the acoustic propagation path from tissue irradiation to acoustic detection. Unfortunately epiphotoacoustic imaging suffers from strong clutter, arising from optical absorption in tissue outside the image plane, and from acoustic backscattering.

SU-E-T-255: A Novel Rectal Obturator for Prostate Radiotherapy Improves the Spatial Distribution of Dose and Reduces the Predicted Risk for Rectal Bleeding and Subjective Sphincter Control.

Purpose: To investigate the effects of an endorectal device during prostate radiotherapy on the spatial distribution of dose to the ano-rectal region and quantify implications for normal-tissue-complication probabilities.

Methods: Twenty-three patients with localised prostate cancer, referred for external beam radiotherapy had 2 CT scans acquired, without and with the rectal obturator (ProSpare) in-situ. For each patient two dose distributions were generated, based on both CT scans.

False-negative MRI biomarkers of tumour response to targeted cancer therapeutics.

Background: Non-invasive quantitative imaging biomarkers are essential for the evaluation of novel targeted therapeutics. Before deployment in clinical trials, such imaging biomarkers require qualification, typically through pre-clinical identification of imaging-pathology correlates.

Methods: First, in investigating imaging biomarkers of invasion, the response of orthotopic murine PC3 prostate xenografts to the Src inhibitor saracatinib was assessed using susceptibility contrast MRI.

Cone beam computed tomography number errors and consequences for radiotherapy planning: an investigation of correction methods.

Purpose: The potential of keV cone beam computed tomography (CBCT) for guiding adaptive replanning is well-known. There are impediments to this, one being CBCT number accuracy. The purpose of this study was to investigate CBCT number correction methods and the affect of residual inaccuracies on dose deposition.

Novel approaches to improve the therapeutic index of head and neck radiotherapy: an analysis of data from the PARSPORT randomised phase III trial.

Purpose: Subjective xerostomia is a common side-effect following radiotherapy for the treatment of head-and-neck cancer. Standard mean dose models previously used to model xerostomia only that partially predict the occurrence of xerostomia. Studies in animal models have suggested that there are regional variations in the radiosensitivity of the parotid glands.

Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

Key issues in early clinical trials of targeted agents include the determination of target inhibition, rational patient selection based on pre-treatment tumour characteristics, and assessment of tumour response in the absence of actual shrinkage. There is accumulating evidence that functional imaging using advanced techniques such as dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), DCE-computerised tomography (CT) and DCE-ultrasound, diffusion weighted-MRI, magnetic resonance spectroscopy and positron emission tomography-CT using various labelled radioactive tracers has the potential to address all three. This article reviews this evidence with examples from trials using targeted agents with established clinical efficacy and summarises the clinical utility of the various techniques.