Comparison of different 2D muscle indexes measured at the level of the 3rd lumbar vertebra in survival prediction in patients with renal cell carcinoma.

BACKGROUND: Low computed tomography (CT)-determined muscle mass, commonly determined with height-adjusted muscle indexes (MIs), predicts worse survival in several cancers and has been suggested as a prognostic assessment tool. Although several MIs measured at the level of the 3rd lumbar vertebra (L3) are commonly used, it remains unestablished how different L3-determined MIs perform in survival prognostication compared to each other. The objective of this study was to investigate the performance of different MIs for survival prognostication in renal cell carcinoma (RCC). METHODS: We retrospectively enrolled 214 consecutive patients with RCC. We determined three L3-MIs (psoas muscle index (PMI), psoas muscle index and erector spinae index (PMI+ESI), and whole skeletal muscle index (SMI)) from preoperative CT scans. Categorization of those with low and normal muscle mass was based on the Youden Index sex-specific MI cut-offs. We determined sensitivity, specificity, and accuracy metrics for predicting 1-year, 5-year, and overall survival (OS) using Cox regression models. RESULTS: Low PMI, PMI+ESI, and SMI significantly predicted decreased 1-year, 5-year, and OS in uni- and multivariate models. PMI+ESI and SMI were more accurate than PMI in males, and PMI and PMI+ESI were more accurate than SMI in females in the prediction of 1-year survival. However, there were no differences in accuracies between MIs in 5-year and OS prediction. INTERPRETATION: PMI+ESI performed well overall in short-term prognostication, but there were no differences between the MIs in long-term prognostication. We recommend the use of PMI+ESI for muscle evaluation, particularly when SMI cannot be evaluated.

Transfer learning for the generalization of artificial intelligence in breast cancer detection: a case-control study.

BACKGROUND: Some researchers have questioned whether artificial intelligence (AI) systems maintain their performance when used for women from populations not considered during the development of the system. PURPOSE: To evaluate the impact of transfer learning as a way of improving the generalization of AI systems in the detection of breast cancer. MATERIAL AND METHODS: This retrospective case-control Finnish study involved 191 women diagnosed with breast cancer and 191 matched healthy controls. We selected a state-of-the-art AI system for breast cancer detection trained using a large US dataset. The selected baseline system was evaluated in two experimental settings. First, we examined our private Finnish sample as an independent test set that had not been considered in the development of the system (unseen population). Second, the baseline system was retrained to attempt to improve its performance in the unseen population by means of transfer learning. To analyze performance, we used areas under the receiver operating characteristic curve (AUCs) with DeLong's test. RESULTS: Two versions of the baseline system were considered: ImageOnly and Heatmaps. The ImageOnly and Heatmaps versions yielded mean AUC values of 0.82±0.008 and 0.88±0.003 in the US dataset and 0.56 (95% CI=0.50-0.62) and 0.72 (95% CI=0.67-0.77) when evaluated in the unseen population, respectively. The retrained systems achieved AUC values of 0.61 (95% CI=0.55-0.66) and 0.69 (95% CI=0.64-0.75), respectively. There was no statistical difference between the baseline system and the retrained system. CONCLUSION: Transfer learning with a small study sample did not yield a significant improvement in the generalization of the system.

Frailty in Late Midlife to Old Age and Its Relationship to Medical Imaging Use and Imaging-related Costs: A Longitudinal Study.

Background Frailty, defined as an increased vulnerability to and impaired recovery from stressors, is common in individuals in late midlife to old age. While frailty predisposes individuals to adverse health outcomes and increased health care utilization, how it impacts imaging service use and related costs remains unclear. Purpose To determine whether frailty is associated with greater use of imaging services and higher imaging-related costs. Materials and Methods This longitudinal study included a subset of participants from the Helsinki Birth Cohort Study who were clinically assessed up to three times from late midlife to old age between August 2001 and September 2018. A frailty index (FI) based on 41 variables was calculated, and an FI of 0.25 or more indicated frailty. Associations of baseline frailty and its rate of change during the study with medical imaging service use and imaging-related costs were assessed using covariate-adjusted negative binomial and other generalized linear models. Results Of the 1995 participants (mean age, 61.5 years ± 2.9 [SD]; 1074 female participants) included in this study, 569 (28.5%) were identified as frail at baseline, and these participants underwent 10 677 (42.4%) of the 25 172 medical imaging examinations among the participants. Compared to participants who were not frail at baseline, participants who were frail at baseline showed increased use of all imaging modalities (incidence rate ratio [IRR], 2.28 [95% CI: 1.97, 2.64]; P < .001) and higher imaging costs (log annual cost, 3.26 [95% CI: 2.36, 4.50]; P < .001). Compared to participants with stable or slow change in frailty (<0.0010 FI units per year), participants with a rapid increase in frailty (>0.0064 FI units per year) from late midlife to old age showed greater use of all medical imaging services, independent of FI at baseline (IRR, 1.82 [95% CI: 1.53, 2.17]; P < .001) and had higher imaging costs (log annual cost, 1.62 [95% CI: 1.30, 2.01)]; P < .001). Conclusion The presence of frailty and its progression rate are associated with increased use of imaging services and higher imaging-related costs. © RSNA, 2023 Supplemental material is available for this article.

Neoadjuvant chemotherapy induces an elevation of tumour apparent diffusion coefficient values in patients with ovarian cancer.

OBJECTIVES: Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). METHODS: We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient's disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. RESULTS: The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71-0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p < 0.001, S-ROIs p < 0.01), and the increase after NACT was associated with sensitivity to platinum-based chemotherapy. The changes in the ADC values of the omental mass were associated with a response to NACT. CONCLUSION: The mean ADC values of the primary tumour increased significantly after NACT in the OC patients, and the amount of increase in omental mass was associated with the response to platinum-based NACT. Our study indicates that quantitative analysis of ADC values with a single slice and a whole tumour ROI placement is a reproducible method that has a potential role in the evaluation of NACT response in patients with OC. TRIAL REGISTRATION: Retrospectively registered (institutional permission code: 5302501; date of the permission: 31.7.2020).

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer.

OBJECTIVES: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. METHODS: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. RESULTS: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. CONCLUSION: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. CLINICAL RELEVANCE STATEMENT: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. KEY POINTS: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI.

The utilization of primary healthcare services among frail older adults - findings from the Helsinki Birth Cohort Study.

BACKGROUND: The impact of frailty on primary healthcare service use, especially general practice office visits and remote contacts, is currently unknown. Further, little is known about the association of frailty with physiotherapy contacts. METHODS: We examined the utilization of primary healthcare services among 1064 participants from the Helsinki Birth Cohort Study between the years 2013 and 2017. Frailty was assessed based on Fried's frailty criteria at mean age of 71.0 (2.7 SD) years in clinical examinations between the years 2011 and 2013. General practice office visits and remote contacts, the total number of general practice contacts, physiotherapy contacts, and the total number of primary healthcare contacts were extracted from a national Finnish register. We analyzed the data with negative binomial regression models. RESULTS: Of the 1064 participants, 37 were frail (3.5%) and 427 pre-frail (40.1%); 600 non-frail (56.4%) served as a reference group. Frailty was associated with general practice office visits (IRR 1.31, 95% CI=1.01-1.69), physiotherapy contacts (IRR 2.97, 95% CI=1.49-5.91) and the total number of primary healthcare contacts (IRR 1.41, 95% CI=1.07-1.85). Pre-frailty predicted the use of general practice remote contacts (IRR 1.39, 95% CI=1.22-1.57) and the total number of general practice contacts (IRR 1.25, 95% CI=1.12-1.40). CONCLUSIONS: Frailty increases the overall primary healthcare service use whereas pre-frailty is associated with the use of general practice services, especially remote contacts. Primary healthcare needs measures to adapt healthcare services based on the needs of rapidly increasing number of pre-frail and frail older adults and should consider preventative interventions against frailty.

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI.

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990-0.997); for breast volume, r = 0.985 (95% CI 0.934-0.994); and for FGT volume, r = 0.979 (95% CI 0.958-0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819-0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630-0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual's breast cancer risk stratification.

Primary and metastatic ovarian cancer: Characterization by 3.0T diffusion-weighted MRI.

OBJECTIVES: We aimed to investigate whether apparent diffusion coefficients (ADCs) measured by 3.0T diffusion-weighted magnetic resonance imaging (DWI) associate with histological aggressiveness of ovarian cancer (OC) or predict the clinical outcome. This prospective study enrolled 40 patients with primary OC, treated 2011-2014. METHODS: DWI was performed prior to surgery. Two observers used whole lesion single plane region of interest (WLsp-ROI) and five small ROIs (S-ROI) to analyze ADCs. Samples from tumours and metastases were collected during surgery. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure the expression of vascular endothelial growth factor (VEGF) and its receptors. RESULTS: The interobserver reliability of ADC measurements was excellent for primary tumours ICC 0.912 (WLsp-ROI). Low ADCs significantly associated with poorly differentiated OC (WLsp-ROI P = 0.035). In primary tumours, lower ADCs significantly associated with high Ki-67 (P = 0.001) and low VEGF (P = 0.001) expression. In metastases, lower ADCs (WLsp-ROI) significantly correlated with low VEGF receptors mRNA levels. ADCs had predictive value; 3-year overall survival was poorer in patients with lower ADCs (WLsp-ROI P = 0.023, S-ROI P = 0.038). CONCLUSION: Reduced ADCs are associated with histological severity and worse outcome in OC. ADCs measured with WLsp-ROI may serve as a prognostic biomarker of OC. KEY POINTS: • Reduced ADCs correlate with prognostic markers: poor differentiation and high Ki-67 expression • ADCs also significantly correlated with VEGF protein expression in primary tumours • Lower ADC values are associated with poorer survival in ovarian cancer • Whole lesion single plane-ROI ADCs may be used as a prognostic biomarker in OC.

Is there a Role for Contrast-enhanced Ultrasound in the Detection and Biopsy of MRI Only Visible Breast Lesions?

BACKGROUND: This study aimed to evaluate the feasibility of contrast-enhanced ultrasound (CEUS) and CEUS-guided interventions in the diagnostics of MRI visible targeted US occult breast lesions. PATIENTS AND METHODS: This retrospective study examined 10 females with 10 occult, MRI only detected breast lesions between July 2014 and April 2017. Targeted second look US followed by CEUS with 2.4 ml of SonoVue® were performed for all of the lesions. After positive CEUS localization the same dose was repeated for confirmation and CEUS-guided interventions were performed. RESULTS: MRI revealed 8 mass lesions with a mean size of 9 mm (range 5-16 mm) and 2 non-mass enhancing lesions of 10 and 20 mm in largest diameters. Targeted US revealed no morphological correlate for the lesions. Five out of 10 lesions (50%) were visible on CEUS. CEUS-guided core biopsy was performed on 4 lesions and 1 was marked with a clip for later surgical removal. Histopathological analysis confirmed 4 of them to be malignant. Three out of 5 nonvisible lesions on CEUS underwent MRI-guided interventions, 1 lesion was scheduled for follow-up as it was non-amenable for MRI biopsy, and 1 lesion was biopsied under US-guidance. Three of these nonvisible lesions on CEUS were confirmed to be malignant. CONCLUSIONS: Based on our preliminary results, CEUS is a feasible tool for detecting many MRI only visible breast lesions, resulting in a more cost effective and less time-consuming practice. It is a more convenient alternative than MRI guided biopsy and has the potential to be included in the diagnostic algorithm which evaluates MRI only visible breast lesions.

Prognostic contribution of mammographic breast density and HER2 overexpression to the Nottingham Prognostic Index in patients with invasive breast cancer.

BACKGROUND: To investigate whether very low mammographic breast density (VLD), HER2, and hormone receptor status holds any prognostic significance within the different prognostic categories of the widely used Nottingham Prognostic Index (NPI). We also aimed to see whether these factors could be incorporated into the NPI in an effort to enhance its performance. METHODS: This study included 270 patients with newly diagnosed invasive breast cancer. Patients with mammographic breast density of <10 % were considered as VLD. In this study, we compared the performance of NPI with and without VLD, HER2, ER and PR. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (0.632+ bootstrap estimator) were used to derive an updated version of NPI. RESULTS: Both mammographic breast density (VLD) (p < 0.001) and HER2 status (p = 0.049) had a clinically significant effect on the disease free survival of patients in the intermediate and high risk groups of the original NPI classification. The incorporation of both factors (VLD and HER2 status) into the NPI provided improved patient outcome stratification by decreasing the percentage of patients in the intermediate prognostic groups, moving a substantial percentage towards the low and high risk prognostic groups. CONCLUSIONS: Very low density (VLD) and HER2 positivity were prognostically significant factors independent of the NPI. Furthermore, the incorporation of VLD and HER2 to the NPI served to enhance its accuracy, thus offering a readily available and more accurate method for the evaluation of patient prognosis.

Incidentally detected enhancing lesions found in breast MRI: analysis of apparent diffusion coefficient and T2 signal intensity significantly improves specificity.

OBJECTIVES: To evaluate the value of adding T2- and diffusion-weighted imaging (DWI) to the BI-RADS® classification in MRI-detected lesions. METHODS: This retrospective study included 112 consecutive patients who underwent 3.0T structural breast MRI with T2- and DWI on the basis of EUSOMA recommendations. Morphological and kinetic features, T2 signal intensity (T2 SI) and apparent diffusion coefficient (ADC) findings were assessed. RESULTS: Thirty-three (29.5 %) patients (mean age 57.0 ± 12.7 years) had 36 primarily MRI-detected incidental lesions of which 16 (44.4 %) proved to be malignant. No single morphological or kinetic feature was associated with malignancy. Both low T2 SI (P = 0.009) and low ADC values (≤0.87 × 10-3 mm2s-1, P < 0.001) yielded high specificity (80.0 %/80.0 %). The BI-RADS classification supplemented with information from DWI and T2-WI improved the diagnostic performance of the BI-RADS classification as sensitivity remained 100 % and specificity improved from 30 % to 65.0 %. The numbers of false positive lesions declined from 39 % (N = 14) to 19 % (N = 7). CONCLUSION: MRI-detected incidental lesions may be challenging to characterize as they have few specific malignancy indicating features. The specificity of MRI can be improved by incorporating T2 SI and ADC values into the BI-RADS assessment. KEY POINTS: • MRI-detected incidental lesions have few specific malignancy indicating features. • ≥ 1 suspicious morphologic or kinetic feature may warrant biopsy. • T2 signal intensity and DWI assessment are feasible in primarily MRI-detected lesions. • T2 SI and DWI assessment improve the BI-RADS specificity in MRI-detected lesions.

Correlation of cerebral small vessel disease burden with outcome after lower extremity amputation.

AIMS: This study assessed whether changes associated with cerebral small vessel disease (CSVD) evaluated from head computed tomography (CT) images captured for non-related clinical purposes predict overall survival (OS), leg salvage (LS), and amputation-free survival (AFS) after lower extremity amputation (LEA). METHODS: We retrospectively included a cohort of 240 patients who had undergone a lower extremity amputation in Tampere University Hospital between the years 2007 and 2020 and had a head CT scan (within one year before amputation). A neuroradiologist graded the white matter lesions (WMLs) and reported infarcts, and the latter's effects on OS, LS, and AFS were evaluated. RESULTS: Altogether, 162 (67.5 %) and 91 (38.1 %) patients had WMLs and infarcts, respectively. Mild/moderate (HR 1.985, CI 95 % 1.317-2.992) and severe (HR 2.259, CI 95 % 1.501-3.399) WMLs and infarcts (HR 1.413, CI 95 % 1.029-1.940) were associated with inferior OS. After a minor amputation, mild/moderate (HR 2.012, CI 95 % 1.054-3.843) and severe (HR 3.879, CI 95 % 2.096-7.180) WMLs were similarly associated with inferior AFS. CONCLUSIONS: Overall, WML and infarcts detected on head CT scans were associated with impaired OS after LEA and AFS after minor LEA. Evaluation of CSVD could provide useful prognostic information for clinicians.

23Na MRI: inter-reader reproducibility of normal fibroglandular sodium concentration measurements at 3 T.

BACKGROUND: To study the reproducibility of 23Na magnetic resonance imaging (MRI) measurements from breast tissue in healthy volunteers. METHODS: Using a dual-tuned bilateral 23Na/1H breast coil at 3-T MRI, high-resolution 23Na MRI three-dimensional cones sequences were used to quantify total sodium concentration (TSC) and fluid-attenuated sodium concentration (FASC). B1-corrected TSC and FASC maps were created. Two readers manually measured mean, minimum and maximum TSC and mean FASC values using two sampling methods: large regions of interest (LROIs) and small regions of interest (SROIs) encompassing fibroglandular tissue (FGT) and the highest signal area at the level of the nipple, respectively. The reproducibility of the measurements and correlations between density, age and FGT apparent diffusion coefficient (ADC) values were evaluatedss. RESULTS: Nine healthy volunteers were included. The inter-reader reproducibility of TSC and FASC using SROIs and LROIs was excellent (intraclass coefficient range 0.945-0.979, p < 0.001), except for the minimum TSC LROI measurements (p = 0.369). The mean/minimum LROI TSC and mean LROI FASC values were lower than the respective SROI values (p < 0.001); the maximum LROI TSC values were higher than the SROI TSC values (p = 0.009). TSC correlated inversely with age but not with FGT ADCs. The mean and maximum FGT TSC and FASC values were higher in dense breasts in comparison to non-dense breasts (p < 0.020). CONCLUSIONS: The chosen sampling method and the selected descriptive value affect the measured TSC and FASC values, although the inter-reader reproducibility of the measurements is in general excellent. RELEVANCE STATEMENT: 23Na MRI at 3 T allows the quantification of TSC and FASC sodium concentrations. The sodium measurements should be obtained consistently in a uniform manner. KEY POINTS: • 23Na MRI allows the quantification of total and fluid-attenuated sodium concentrations (TSC/FASC). • Sampling method (large/small region of interest) affects the TSC and FASC values. • Dense breasts have higher TSC and FASC values than non-dense breasts. • The inter-reader reproducibility of TSC and FASC measurements was, in general, excellent. • The results suggest the importance of stratifying the sodium measurements protocol.

Reduced temporal muscle thickness predicts shorter survival in patients undergoing chronic subdural haematoma drainage.

BACKGROUND: Chronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty - its key component, low muscle mass, can be assessed using cross-sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage. METHODS: We retrospectively identified all patients who underwent CSDH drainage within 1 year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival. RESULTS: One hundred and eighty-eight (122, 65% males) patients (median age 78 years, IQR 70-85 years) were included. Thirty-four (18%) patients died within 2 years, and 51 (27%) died at a median follow-up of 39 months (IQR 34-42 months). Intra- and inter-observer reliability of TMT measurements was good-to-excellent (ICC 0.85-0.97, P < 0.05). TMT decreased with age (Pearson's r = -0.38, P < 0.001). Females had lower TMT than males (P < 0.001). The optimal TMT cut-off values for predicting two-year survival were 4.475 mm for males and 3.125 mm for females. TMT below these cut-offs was associated with shorter survival in both univariate (HR 3.24, 95% CI 1.85-5.67) and multivariate (HR 1.86, 95% CI 1.02-3.36) analyses adjusted for age, ASA grade and bleed size. The effect of TMT on mortality was not mediated by age. CONCLUSIONS: In patients with CSDH, TMT measurements from preoperative imaging were reliable and contained prognostic information supplemental to previously known predictors of poor outcomes.

Hyperpolarised 13C-MRI using 13C-pyruvate in breast cancer: A review.

Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (13C)-MRI using probes, i.e., endogenously found molecules that are labeled with 13C. Hyperpolarisation of the 13C label increases the sensitivity to a level that allows dynamic imaging of the distribution and metabolism of the probes. Dynamic imaging of [1-13C]pyruvate metabolism is of particular biological interest in cancer because of the Warburg effect resulting in the intratumoural accumulation of [1-13C]pyruvate and conversion to [1-13C]lactate. Numerous preclinical studies in breast cancer and other tumours have shown that hyperpolarised 13C-pyruvate has potential for metabolic phenotyping and response assessment at earlier timepoints than the current clinical imaging techniques allow. The clinical feasibility of hyperpolarised 13C-MRI after the injection of pyruvate in patients with breast cancer has now been demonstrated, with increased 13C-label exchange between pyruvate and lactate present in higher grade tumours with associated increased expression of the monocarboxylate transporter 1 (MCT1), the transmembrane transporter mediating intracellular pyruvate uptake, and lactate dehydrogenase (LDH) as the enzyme catalysing the conversion of pyruvate to lactate. Furthermore, a study in patients with breast cancer undergoing neoadjuvant chemotherapy suggested that early changes in 13C-label exchange can distinguish between patients who reach pathologic complete response (pCR) and those who do not. This review summarises the current literature on preclinical and clinical research on hyperpolarised 13C-MRI with [1-13C]-pyruvate in breast cancer imaging.

Psychiatric medications and the risk of autoimmune and immune-mediated inflammatory diseases: A systematic review and meta-analysis of observational studies.

BACKGROUND: Pharmacovigilance reports have suggested that certain commonly used medications may trigger autoimmune diseases (ADs) and immune-mediated inflammatory diseases (IMIDs). We systematically reviewed the literature to evaluate whether psychiatric medication use is associated with ADs and IMIDs. METHODS: The protocol was registered in PROSPERO (CRD42022296524) before the start of the study. We searched Medline Ovid and Scopus up to November 28th, 2021, for comparative studies, with any psychiatric medication as exposure and ADs and IMIDs as outcomes. Meta-analysis was performed using DerSimonian-Laird random-effects modeling. The PRISMA 2020 guidelines were followed in reporting. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence using GRADE. RESULTS: There were 7,265 citations from which 31 studies were eligible, all from high-income countries, covering 15 distinct immune diseases. The evidence for the association between selective serotonin reuptake inhibitor (SSRI) use and higher risk of microscopic colitis (meta-OR 2.60, 95% CI 1.05-6.39, I2 97.5%, 6 studies) was of low certainty. A subgroup analysis by the histological type of microscopic colitis showed a statistically significant association only with lymphocytic colitis (meta-OR 2.88, 95% CI 2.60-3.18, I2 00.00%, three studies). In two case-control studies, SSRI use had no significant association with psoriasis (meta-OR 0.80, 95% CI 0.58-1.10, I2 82.4%). The risk of acute pancreatitis was slightly increased with exposure to SSRIs (meta-OR 1.13, 95% CI 1.01-1.26, I2 00.0%), as was the risk of bullous pemphigoid after exposure to antipsychotics (meta-OR 1.79, 95% CI 1.17-2.73, I2 0%). CONCLUSIONS: We reviewed the literature on whether psychiatric medications associate with the risk of ADs and IMIDs and concluded that, despite several signals, the credibility of evidence remains low at best. Prospective cohort studies would be needed as the next step to confirm the suggestions of increased risk.

Association between Computed Tomography-Determined Loss of Muscle Mass and Impaired Three-Month Survival in Frail Older Adults with Cancer.

As patients with solid (non-hematological) cancers and a life expectancy of <3 months rarely benefit from oncological treatment, we examined whether the CT-determined loss of muscle mass is associated with an impaired 3-month overall survival (OS) in frail ≥75-year-old patients with cancer. Frailty was assessed with G8-screening and comprehensive geriatric assessment in older adults at risk of frailty. The L3-level skeletal (SMI) and psoas (PMI) muscle indexes were determined from routine CT scans. Established and optimized SMI and PMI cut-offs were used. In the non-curative treatment group (n = 58), 3-month OS rates for normal and low SMI were 95% and 64% (HR 9.28; 95% CI 1.2-71) and for PMI 88%, and 60%, respectively (HR 4.10; 1.3-13). A Cox multivariable 3-month OS model showed an HR of 10.7 (1.0-110) for low SMI, 2.34 (0.6-9.8) for ECOG performance status 3-4, 2.11 (0.5-8.6) for clinical frailty scale 5-9, and 0.57 (0.1-2.8) for males. The 24-month OS rates in the curative intent group (n = 21) were 91% and 38% for the normal and low SMI groups, respectively. In conclusion, CT-determined low muscle mass is independently associated with an impaired 3-month OS and, alongside geriatric assessment, could aid in oncological versus best supportive care decision-making in frail patients with non-curable cancers.

Dynamic contrast-enhanced MRI to characterize angiogenesis in primary epithelial ovarian cancer: An exploratory study.

PURPOSE: Angiogenesis is essential for tumor growth. Currently, there are no established imaging biomarkers to show angiogenesis in tumor tissue. The aim of this prospective study was to evaluate whether semiquantitative and pharmacokinetic DCE-MRI perfusion parameters could be used to assess angiogenesis in epithelial ovarian cancer (EOC). METHOD: We enrolled 38 patients with primary EOC treated in 2011-2014. DCE-MRI was performed with a 3.0 T imaging system before the surgical treatment. Two different sizes of ROI were used to evaluate semiquantitative and pharmacokinetic DCE perfusion parameters: a large ROI (L-ROI) covering the whole primary lesion on one plane and a small ROI (S-ROI) covering a small solid, highly enhancing focus. Tissue samples from tumors were collected during the surgery. Immunohistochemistry was used to measure the expression of vascular endothelial growth factor (VEGF), its receptors (VEGFRs) and to analyse microvascular density (MVD) and the number of microvessels. RESULTS: VEGF expression correlated inversely with Ktrans (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.390, (p = 0.010)), Ve (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.412 (p = 0.006)) and Vp (L-ROI, r = -0.388 (p = 0.011), S-ROI, r = -0.339 (p = 0.028)) values in EOC. Higher VEGFR-2 correlated with lower DCE parameters Ktrans (L-ROI, r = -0.311 (p = 0.040), S-ROI, r = -0.337 (p = 0.025)) and Ve (L-ROI, r = -0.305 (p = 0.044), S-ROI, r = -0.355 (p = 0.018)). We also found that MVD and the number of microvessels correlated positively with AUC, Peak and WashIn values. CONCLUSIONS: We observed that several DCE-MRI parameters correlated with VEGF and VEGFR-2 expression and MVD. Thus, both semiquantitative and pharmacokinetic perfusion parameters of DCE-MRI represent promising tools for the assessment of angiogenesis in EOC.