The use of hyperpolarised 13 C-MRI in clinical body imaging to probe cancer metabolism

Abstract: Metabolic reprogramming is one of the hallmarks of cancer and includes the Warburg effect, which is exhibited by many tumours. This can be exploited by positron emission tomography (PET) as part of routine clinical cancer imaging. However, an emerging and alternative method to detect altered metabolism is carbon-13 magnetic resonance imaging (MRI) following injection of hyperpolarised [1-13C]pyruvate. The technique increases the signal-to-noise ratio for the detection of hyperpolarised 13C-labelled metabolites by several orders of magnitude and facilitates the dynamic, noninvasive imaging of the exchange of 13C-pyruvate to 13C-lactate over time. The method has produced promising preclinical results in the area of oncology and is currently being explored in human imaging studies. The first translational studies have demonstrated the safety and feasibility of the technique in patients with prostate, renal, breast and pancreatic cancer, as well as revealing a successful response to treatment in breast and prostate cancer patients at an earlier stage than multiparametric MRI. This review will focus on the strengths of the technique and its applications in the area of oncological body MRI including noninvasive characterisation of disease aggressiveness, mapping of tumour heterogeneity, and early response assessment. A comparison of hyperpolarised 13C-MRI with state-of-the-art multiparametric MRI is likely to reveal the unique additional information and applications offered by the technique

Breast MRI radiomics and machine learning radiomics-based predictions of response to neoadjuvant chemotherapy -- how are they affected by variations in tumour delineation?

Manual delineation of volumes of interest (VOIs) by experts is considered the gold-standard method in radiomics analysis. However, it suffers from inter- and intra-operator variability. A quantitative assessment of the impact of variations in these delineations on the performance of the radiomics predictors is required to develop robust radiomics based prediction models. In this study, we developed radiomics models for the prediction of pathological complete response to neoadjuvant chemotherapy in patients with two different breast cancer subtypes based on contrast-enhanced magnetic resonance imaging acquired prior to treatment (baseline MRI scans). Different mathematical operations such as erosion, smoothing, dilation, randomization, and ellipse fitting were applied to the original VOIs delineated by experts to simulate variations of segmentation masks. The effects of such VOI modifications on various steps of the radiomics workflow, including feature extraction, feature selection, and prediction performance, were evaluated. Using manual tumor VOIs and radiomics features extracted from baseline MRI scans, an AUC of up to 0.96 and 0.89 was achieved for human epidermal growth receptor 2 positive and triple-negative breast cancer, respectively. For smoothing and erosion, VOIs yielded the highest number of robust features and the best prediction performance, while ellipse fitting and dilation lead to the lowest robustness and prediction performance for both breast cancer subtypes. At most 28% of the selected features were similar to manual VOIs when different VOI delineation data were used. Differences in VOI delineation affects different steps of radiomics analysis, and their quantification is therefore important for development of standardized radiomics research

A Simple Ultrasound Based Classification Algorithm Allows Differentiation of Benign from Malignant Breast Lesions by Using Only Quantitative Parameters.

PURPOSE: We hypothesized that different quantitative ultrasound (US) parameters may be used as complementary diagnostic criteria and aimed to develop a simple classification algorithm to distinguish benign from malignant breast lesions and aid in the decision to perform biopsy or not. PROCEDURES: One hundred twenty-four patients, each with one biopsy-proven, sonographically evident breast lesion, were included in this prospective, IRB-approved study. Each lesion was examined with B-mode US, Color/Power Doppler US and elastography (Acoustic Radiation Force Impulse-ARFI). Different quantitative parameters were recorded for each technique, including pulsatility (PI) and resistive Index (RI) for Doppler US and lesion maximum, intermediate, and minimum shear wave velocity (SWVmax, SWVinterm, and SWVmin) as well as lesion-to-fat SWV ratio for ARFI. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic performance of each quantitative parameter. Classification analysis was performed using the exhaustive chi-squared automatic interaction detection method. Results include the probability for malignancy for every descriptor combination in the classification algorithm. RESULTS: Sixty-five lesions were malignant and 59 benign. Out of all quantitative indices, maximum SWV (SWVmax), and RI were included in the classification algorithm, which showed a depth of three ramifications (SWVmax ≤ or > 3.16; if SWVmax ≤ 3.16 then RI ≤ 0.66, 0.66-0.77 or > 0.77; if RI ≤ 0.66 then SWVmax ≤ or > 2.71). The classification algorithm leads to an AUC of 0.887 (95 % CI 0.818-0.937, p < 0.0001), a sensitivity of 98.46 % (95 % CI 91.7-100 %), and a specificity of 61.02 % (95 % CI 47.4-73.5 %). By applying the proposed algorithm, a false-positive biopsy could have been avoided in 61 % of the cases. CONCLUSIONS: A simple classification algorithm incorporating two quantitative US parameters (SWVmax and RI) shows a high diagnostic performance, being able to accurately differentiate benign from malignant breast lesions and lower the number of unnecessary breast biopsies in up to 60 % of all cases, avoiding any subjective interpretation bias

Virtual Touch IQ elastography reduces unnecessary breast biopsies by applying quantitative "rule-in" and "rule-out" threshold values.

Our purpose was to evaluate Virtual Touch IQ (VTIQ) elastography and identify quantitative "rule-in" and "rule-out" thresholds for the probability of malignancy, which can help avoid unnecessary breast biopsies. 189 patients with 196 sonographically evident lesions were included in this retrospective, IRB-approved study. Quantitative VTIQ images of each lesion measuring the respective maximum Shear Wave Velocity (SWV) were obtained. Paired and unpaired, non-parametric statistics were applied for comparisons as appropriate. ROC-curve analysis was used to analyse the diagnostic performance of VTIQ and to specify "rule-in" and "rule-out" thresholds for the probability of malignancy. The standard of reference was either histopathology or follow-up stability for >24 months. 84 lesions were malignant and 112 benign. Median SWV of benign lesions was significantly lower than that of malignant lesions (p 98% with a concomitant significant (p = 0.032) reduction in false positive cases of almost 15%, whereas a "rule-in" threshold of 6.5 m/s suggested a probability of malignancy of >95%. In conclusion, VTIQ elastography accurately differentiates malignant from benign breast lesions. The application of quantitative "rule-in" and "rule-out" thresholds is feasible and allows reduction of unnecessary benign breast biopsies by almost 15%

Breast lesion detection and characterization with contrast-enhanced magnetic resonance imaging: Prospective randomized intraindividual comparison of gadoterate meglumine (0.15 mmol/kg) and gadobenate dimeglumine (0.075 mmol/kg) at 3T.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (CE-MRI) of the breast is highly sensitive for breast cancer detection. Multichannel coils and 3T scanners can increase signal, spatial, and temporal resolution. In addition, the T1 -reduction effect of a gadolinium-based contrast agent (GBCA) is higher at 3T. Thus, it might be possible to reduce the dose of GBCA at 3T without losing diagnostic information. PURPOSE: To compare a three-quarter (0.075 mmol/kg) dose of the high-relaxivity GBCA gadobenate dimeglumine, with a 1.5-fold higher than on-label dose (0.15 mmol/kg) of gadoterate meglumine for breast lesion detection and characterization at 3T CE-MRI. STUDY TYPE: Prospective, randomized, intraindividual comparative study. POPULATION: Eligible were patients with imaging abnormalities (BI-RADS 0, 4, 5) on conventional imaging. Each patient underwent two examinations, 24-72 hours apart, one with 0.075 mmol/kg gadobenate and the other with 0.15 mmol/kg gadoterate administered in a randomized order. In all, 109 patients were prospectively recruited. FIELD STRENGTH/SEQUENCE: 3T MRI with a standard breast protocol (dynamic-CE, T2 w-TSE, STIR-T2 w, DWI). ASSESSMENT: Histopathology was the standard of reference. Three blinded, off-site breast radiologists evaluated the examinations using the BI-RADS lexicon. STATISTICAL TESTS: Lesion detection, sensitivity, specificity, and diagnostic accuracy were calculated per-lesion and per-region, and compared by univariate and multivariate analysis (Generalized Estimating Equations, GEE). RESULTS: Five patients were excluded, leaving 104 women with 142 histologically verified breast lesions (109 malignant, 33 benign) available for evaluation. Lesion detection with gadobenate (84.5-88.7%) was not inferior to gadoterate (84.5-90.8%) (P ≥ 0.165). At per-region analysis, gadobenate demonstrated higher specificity (96.4-98.7% vs. 92.6-97.3%, P ≤ 0.007) and accuracy (96.3-97.8% vs. 93.6-96.1%, P ≤ 0.001) compared with gadoterate. Multivariate analysis demonstrated superior, reader-independent diagnostic accuracy with gadobenate (odds ratio = 1.7, P < 0.001 using GEE). DATA CONCLUSION: A 0.075 mmol/kg dose of the high-relaxivity contrast agent gadobenate was not inferior to a 0.15 mmol/kg dose of gadoterate for breast lesion detection. Gadobenate allowed increased specificity and accuracy. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1157-1165

Correction: Type 2 Endoleaks: The Diagnostic Performance of Non-Specialized Readers on Arterial and Venous Phase Multi-Slice CT Angiography.

[This corrects the article DOI: 10.1371/journal.pone.0149725.]

Type 2 Endoleaks: The Diagnostic Performance of Non-Specialized Readers on Arterial and Venous Phase Multi-Slice CT Angiography.

PURPOSE: To define the diagnostic precision of non-specialized readers in the detection of type 2 endoleaks (T2EL) in arterial versus venous phase acquisitions, and to evaluate an approach for radiation dose reduction. METHODS: The pre-discharge and final follow-up multi-slice CT angiographies of 167 patients were retrospectively analyzed. Image data were separated into an arterial and a venous phase reading set. Two radiology residents assessed the reading sets for the presence of a T2EL, feeding vessels, and aneurysm sac size. Findings were compared with a standard of reference established by two experts in interventional radiology. The effective dose was calculated. RESULTS: Overall, experts detected 131 T2ELs, and 331 feeding vessels in 334 examinations. Persistent T2ELs causing aneurysm sac growth > 5 mm were detected in 20 patients. Radiation in arterial and venous phases contributed to a mean of 58.6% and 39.0% of the total effective dose. Findings of reader 1 and 2 showed comparable sensitivities in arterial sets of 80.9 versus 85.5 (p = 0.09), and in venous sets of 73.3 versus 79.4 (p = 0.15), respectively. Reader 1 and 2 achieved a significant higher detection rate of feeding vessels with arterial compared to venous set (p = 0.04, p < 0.01). Both readers correctly identified T2ELs with growing aneurysm sac in all cases, independent of the acquisition phase. CONCLUSION: Arterial acquisitions enable non-specialized readers an accurate detection of T2ELs, and a significant better identification of feeding vessels. Based on our results, it seems reasonable to eliminate venous phase acquisitions

Calibrating Ensembles for Scalable Uncertainty Quantification in Deep Learning-based Medical Segmentation

Uncertainty quantification in automated image analysis is highly desired in many applications. Typically, machine learning models in classification or segmentation are only developed to provide binary answers; however, quantifying the uncertainty of the models can play a critical role for example in active learning or machine human interaction. Uncertainty quantification is especially difficult when using deep learning-based models, which are the state-of-the-art in many imaging applications. The current uncertainty quantification approaches do not scale well in high-dimensional real-world problems. Scalable solutions often rely on classical techniques, such as dropout, during inference or training ensembles of identical models with different random seeds to obtain a posterior distribution. In this paper, we show that these approaches fail to approximate the classification probability. On the contrary, we propose a scalable and intuitive framework to calibrate ensembles of deep learning models to produce uncertainty quantification measurements that approximate the classification probability. On unseen test data, we demonstrate improved calibration, sensitivity (in two out of three cases) and precision when being compared with the standard approaches. We further motivate the usage of our method in active learning, creating pseudo-labels to learn from unlabeled images and human-machine collaboration

Tissue-specific and interpretable sub-segmentation of whole tumour burden on CT images by unsupervised fuzzy clustering.

BACKGROUND: Cancer typically exhibits genotypic and phenotypic heterogeneity, which can have prognostic significance and influence therapy response. Computed Tomography (CT)-based radiomic approaches calculate quantitative features of tumour heterogeneity at a mesoscopic level, regardless of macroscopic areas of hypo-dense (i.e., cystic/necrotic), hyper-dense (i.e., calcified), or intermediately dense (i.e., soft tissue) portions. METHOD: With the goal of achieving the automated sub-segmentation of these three tissue types, we present here a two-stage computational framework based on unsupervised Fuzzy C-Means Clustering (FCM) techniques. No existing approach has specifically addressed this task so far. Our tissue-specific image sub-segmentation was tested on ovarian cancer (pelvic/ovarian and omental disease) and renal cell carcinoma CT datasets using both overlap-based and distance-based metrics for evaluation. RESULTS: On all tested sub-segmentation tasks, our two-stage segmentation approach outperformed conventional segmentation techniques: fixed multi-thresholding, the Otsu method, and automatic cluster number selection heuristics for the K-means clustering algorithm. In addition, experiments showed that the integration of the spatial information into the FCM algorithm generally achieves more accurate segmentation results, whilst the kernelised FCM versions are not beneficial. The best spatial FCM configuration achieved average Dice similarity coefficient values starting from 81.94±4.76 and 83.43±3.81 for hyper-dense and hypo-dense components, respectively, for the investigated sub-segmentation tasks. CONCLUSIONS: The proposed intelligent framework could be readily integrated into clinical research environments and provides robust tools for future radiomic biomarker validation