The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI

Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design.

BACKGROUND: The detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of (18)F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography ((18)F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT. PATIENTS AND METHODS: An adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with (18)F-NaF PET/CT and (99m)Tc-labelled methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system. RESULTS: Seventy-seven lesions were diagnosed as malignant: 100% were identified by (18)F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by (18)F-NaF PET/CT. On an individual patient basis, (18)F-NaF PET/CT detected more RCC metastases than (99m)Tc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUV mean and SUV max) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001). CONCLUSIONS: (18)F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases.This work was supported by Cancer Research UK [grant number C19212/A16628]. The authors also received research support from the National Institute of Health Research Cambridge Biomedical Research Centre, Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, and the Cambridge Experimental Cancer Medicine Centre. The research has also been partly funded by a generous donation from the family and friends of a patient.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/annonc/mdv28

Unsupervised Segmentation of 5D Hyperpolarized Carbon-13 MRI Data Using a Fuzzy Markov Random Field Model

Hyperpolarized MRI with 13C-labelled compounds is an emerging clinical technique allowing in vivo metabolic processes to be characterized non-invasively. Accurate quantification of 13C data, both for clinical and research purposes, typically relies on the use of region-of-interest analysis to detect and compare regions of altered metabolism. However, it is not clear how this should be determined from the five-dimensional data produced and most standard methodologies are unable to exploit the multidimensional nature of the data. Here we propose a solution to the novel problem of 13C image segmentation using a hybrid Markov random field model with continuous fuzzy logic. The algorithm fully utilizes the multi-dimensional data format in order to classify each voxel into one of six distinct classes based on its metabolic characteristics. Bayesian priors fully incorporate spatial, temporal and ratiometric contextual information whilst image contrast from multiple spectral dimensions are considered concurrently by using an analogy from color image segmentation. Performance of the algorithm is demonstrated on in silico data where the superiority of the approach over a reference thresholding method is consistently observed. Application to in vivo animal data from a pre-clinical subcutaneous tumor model illustrates the ability of the MRF algorithm to successfully detect tumor location whilst avoiding image artefacts. This work has the potential to assist the analysis of human hyperpolarized 13C data in the future.CJD is jointly funded by the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre and GlaxoSmithKline (GSK). The authors acknowledge further research support from Cancer Research UK (C19212/A911376, C19212/A16628), the Cancer Research UK/Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, the CRUK Cambridge Centre and Cambridge Experimental Cancer Medicine Centre

MRI techniques for immunotherapy monitoring

Supplementary materials: supplementary data are available online at: https://jitc.bmj.com/content/10/9/e004708#supplementary-materials .Correction: MRI techniques for immunotherapy monitoring, https://doi.org/10.1136/jitc-2022-004708corr1 . Lau D, Corrie PG, Gallagher FAMRI techniques for immunotherapy monitoring. J Immunother Cancer 2022;10:e004708. doi: 10.1136/jitc-2022-004708. The author Ferdia A Gallagher has had the following affiliation added: Cancer Research UK Cambridge Centre, University of Cambridge.MRI is a widely available clinical tool for cancer diagnosis and treatment monitoring. MRI provides excellent soft tissue imaging, using a wide range of contrast mechanisms, and can non-invasively detect tissue metabolites. These approaches can be used to distinguish cancer from normal tissues, to stratify tumor aggressiveness, and to identify changes within both the tumor and its microenvironment in response to therapy. In this review, the role of MRI in immunotherapy monitoring will be discussed and how it could be utilized in the future to address some of the unique clinical questions that arise from immunotherapy. For example, MRI could play a role in identifying pseudoprogression, mixed response, T cell infiltration, cell tracking, and some of the characteristic immune-related adverse events associated with these agents. The factors to be considered when developing MRI imaging biomarkers for immunotherapy will be reviewed. Finally, the advantages and limitations of each approach will be discussed, as well as the challenges for future clinical translation into routine clinical care. Given the increasing use of immunotherapy in a wide range of cancers and the ability of MRI to detect the microstructural and functional changes associated with successful response to immunotherapy, the technique has great potential for more widespread and routine use in the future for these applications.DL is supported by a Worldwide Cancer Research Fund (20–0229) and a Cancer Research UK Oxford Centre Development Fund (CRUKDF-DL; C5255/A18085) at the University of Oxford and was a former radiology PhD scholar funded by CRUK (C9685/A25177) and Cambridge Trust at the University of Cambridge on developing immuno-oncology imaging methods and imaging biomarkers of response to cancer immunotherapy. PGC has research funding from CRUK (C7535/A27717), NIHR Efficacy and Mechanism Evaluation (EME NIHR130047) and Pierre Fabre (N/A). FAG has funding from CRUK (C19212/A27150; C19212/A16628), the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215–20014), the Cambridge Experimental Cancer Medicine Centre & CRUK Cambridge Centre (C9685/A25177), Addenbrooke’s Charitable Trust (N/A), the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215–20014) and the Cambridge University Hospitals National Health Service (NHS) Foundation

Clinical significance of prostate (18)F-labelled fluorodeoxyglucose uptake on positron emission tomography/computed tomography: A five-year review

AIM: To determine the significance and need for investigation of incidental prostatic uptake in men undergoing (18)F-labelled fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for other indications. METHODS: Hospital databases were searched over a 5-year period for patients undergoing both PET/CT and prostate magnetic resonance imaging (MRI). For the initial analysis, the prostate was divided into six sectors and suspicious or malignant sectors were identified using MRI and histopathology reports respectively. Maximum and mean (18)F-FDG standardised uptake values were measured in each sector by an investigator blinded to the MRI and histopathology findings. Two age-matched controls were selected per case. Results were analysed using a paired t-test and one-way ANOVA. For the second analysis, PET/CT reports were searched for prostatic uptake reported incidentally and these patients were followed up. RESULTS: Over a 5-year period, 15 patients underwent both PET/CT and MRI and had biopsy-proven prostate cancer. Malignant prostatic sectors had a trend to higher (18)F-FDG uptake than benign sectors, however this was neither clinically nor statistically significant (3.13 ± 0.58 vs 2.86 ± 0.68, P > 0.05). (18)F-FDG uptake showed no correlation with the presence or histopathological grade of tumour. (18)F-FDG uptake in cases with prostate cancer was comparable to that from age-matched controls. Forty-six (1.6%) of 2846 PET/CTs over a 5-year period reported incidental prostatic uptake. Of these, 18 (0.6%) were investigated by PSA, 9 (0.3%) were referred to urology, with 3 (0.1%) undergoing MRI and/or biopsy. No cases of prostate cancer were diagnosed in patients with incidental (18)F-FDG uptake in our institute over a 5-year period. CONCLUSION: (18)F-FDG uptake overlaps significantly between malignant and benign prostatic conditions. Subsequent patient management was not affected by the reporting of incidental focal prostatic uptake in this cohort

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

Supplementary Information is available online at: https://link.springer.com/article/10.1007/s11307-021-01649-2#Sec15 .Neutrophils are the first line of defense against pathogens and abnormal cells. They regulate many biological processes such as infections and inflammation. Increasing evidence demonstrated a role for neutrophils in cancer, where different subpopulations have been found to possess both pro- or anti-tumorigenic functions in the tumor microenvironment. In this review, we discuss the phenotypic and functional diversity of neutrophils in cancer, their prognostic significance, and therapeutic relevance in human and preclinical models. Molecular imaging methods are increasingly used to probe neutrophil biology in vivo, as well as the cellular changes that occur during tumor progression and over the course of treatment. This review will discuss the role of neutrophil imaging in oncology and the lessons that can be drawn from imaging in infectious diseases and inflammatory disorders. The major factors to be considered when developing imaging techniques and biomarkers for neutrophils in cancer are reviewed. Finally, the potential clinical applications and the limitations of each method are discussed, as well as the challenges for future clinical translation.The researchers are funded by Cancer Research UK (CRUK) (C19212/A16628, C19212/A911376), the CRUK Cambridge Centre (C9685/A25177), a Cambridge Commonwealth, European and International Trust PhD Scholarship, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (RG85317), and GlaxoSmithKline

Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized C-Pyruvate

BACKGROUND: The use of in vivo (13)C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active (13)C substrates, allowing for rapid assessment of (13)C metabolism in vivo. The present study applied hyperpolarized (13)C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. PROCEDURES: [1-(13)C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). RESULTS: Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased (13)C-alanine levels (P < 0.01) compared to normal. CONCLUSIONS: This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology

Case-finding of dementia in general practice and effects of subsequent collaborative care; design of a cluster RCT

<p>Abstract</p> <p>Background</p> <p>In the primary care setting, dementia is often diagnosed relatively late in the disease process. Case finding and proactive collaborative care may have beneficial effects on both patient and informal caregiver by clarifying the cause of cognitive decline and changed behaviour and by enabling support, care planning and access to services.</p> <p>We aim to improve the recognition and diagnosis of individuals with dementia in general practice. In addition to this diagnostic aim, the effects of case finding and subsequent care on the mental health of individuals with dementia and the mental health of their informal carers are explored.</p> <p>Methods and design</p> <p>Design: cluster randomised controlled trial with process evaluation.</p> <p>Participants: 162 individuals ≥ 65 years, in 15 primary care practices, in whom GPs suspect cognitive impairment, but without a dementia diagnosis.</p> <p>Intervention; case finding and collaborative care: 2 trained practice nurses (PNs) invite all patients with suspected cognitive impairment for a brief functional and cognitive screening. If the cognitive tests are supportive of cognitive impairment, individuals are referred to their GP for further evaluation. If dementia is diagnosed, a comprehensive geriatric assessment takes place to identify other relevant geriatric problems that need to be addressed. Furthermore, the team of GP and PN provide information and support.</p> <p>Control: GPs provide care and diagnosis as usual.</p> <p>Main study parameters: after 12 months both groups are compared on: 1) incident dementia (and MCI) diagnoses and 2) patient and caregiver quality of life (QoL-AD; EQ5D) and mental health (MH5; GHQ 12) and caregiver competence to care (SSCQ). The process evaluation concerns facilitating and impeding factors to the implementation of this intervention. These factors are assessed on the care provider level, the care recipient level and on the organisational level.</p> <p>Discussion</p> <p>This study will provide insight into the diagnostic yield and the clinical effects of case finding and collaborative care for individuals with suspected cognitive impairment, compared to usual care. A process evaluation will give insight into the feasibility of this intervention.</p> <p>The first results are expected in the course of 2013.</p> <p>Trial registration</p> <p>NTR3389</p

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology

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Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse.

We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed