Integrating Artificial Intelligence Tools in the Clinical Research Setting: The Ovarian Cancer Use Case.

Artificial intelligence (AI) methods applied to healthcare problems have shown enormous potential to alleviate the burden of health services worldwide and to improve the accuracy and reproducibility of predictions. In particular, developments in computer vision are creating a paradigm shift in the analysis of radiological images, where AI tools are already capable of automatically detecting and precisely delineating tumours. However, such tools are generally developed in technical departments that continue to be siloed from where the real benefit would be achieved with their usage. Significant effort still needs to be made to make these advancements available, first in academic clinical research and ultimately in the clinical setting. In this paper, we demonstrate a prototype pipeline based entirely on open-source software and free of cost to bridge this gap, simplifying the integration of tools and models developed within the AI community into the clinical research setting, ensuring an accessible platform with visualisation applications that allow end-users such as radiologists to view and interact with the outcome of these AI tools.

Assessment of deep learning-based reconstruction on T2-weighted and diffusion-weighted prostate MRI image quality.

PURPOSE: To evaluate the impact of a commercially available deep learning-based reconstruction (DLR) algorithm with varying combinations of DLR noise reduction settings and imaging parameters on quantitative and qualitative image quality, PI-RADS classification and examination time in prostate T2-weighted (T2WI) and diffusion-weighted (DWI) imaging. METHOD: Forty patients were included. Standard-of-care (SoC) prostate MRI sequences including T2WI and DWI were reconstructed without and with different DLR de-noising levels (low, medium, high). In addition, faster T2WI(Fast) and DWI(Fast) sequences, and a higher resolution T2WI(HR) sequence were evaluated. Quantitative analysis included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values. Two radiologists performed qualitative analysis, independently evaluating imaging datasets using 5-point scoring scales for image quality and artifacts. PI-RADS category assignment was also performed by the more experienced radiologist. RESULTS: All DLR levels resulted in significantly higher SNR and CNR compared to the DLR(off) acquisitions. DLR allowed the acquisition time to be reduced by 33% for T2WI(Fast) and 49% for DWI(Fast) compared to SoC, without affecting image quality, whilst T2WI(HR) with DLR allowed for a 73% increase in spatial resolution in the phase encode direction compared to SoC. The inter-reader agreement for image quality and artifact scores was substantial for all subjective measurements on T2WI and DWI. The T2WI(Fast) protocol with DLR(medium) and DWI(Fast) with DLR(low) received the highest qualitative quality score. CONCLUSION: DLR can reduce T2WI and DWI acquisition time and increase SNR and CNR without compromising image quality or altering PI-RADS classification.

PET/MRI of hypoxia and vascular function in ER-positive breast cancer: correlations with immunohistochemistry.

OBJECTIVES: To explore the relationship between indices of hypoxia and vascular function from 18F-fluoromisonidazole ([18F]-FMISO)-PET/MRI with immunohistochemical markers of hypoxia and vascularity in oestrogen receptor-positive (ER +) breast cancer. METHODS: Women aged > 18 years with biopsy-confirmed, treatment-naïve primary ER + breast cancer underwent [18F]-FMISO-PET/MRI prior to surgery. Parameters of vascular function were derived from DCE-MRI using the extended Tofts model, whilst hypoxia was assessed using the [18F]-FMISO influx rate constant, Ki. Histological tumour sections were stained with CD31, hypoxia-inducible factor (HIF)-1α, and carbonic anhydrase IX (CAIX). The number of tumour microvessels, median vessel diameter, and microvessel density (MVD) were obtained from CD31 immunohistochemistry. HIF-1α and CAIX expression were assessed using histoscores obtained by multiplying the percentage of positive cells stained by the staining intensity. Regression analysis was used to study associations between imaging and immunohistochemistry variables. RESULTS: Of the lesions examined, 14/22 (64%) were ductal cancers, grade 2 or 3 (19/22; 86%), with 17/22 (77%) HER2-negative. [18F]-FMISO Ki associated negatively with vessel diameter (p = 0.03), MVD (p = 0.02), and CAIX expression (p = 0.002), whilst no significant relationships were found between DCE-MRI pharmacokinetic parameters and immunohistochemical variables. HIF-1α did not significantly associate with any PET/MR imaging indices. CONCLUSION: Hypoxia measured by [18F]-FMISO-PET was associated with increased CAIX expression, low MVD, and smaller vessel diameters in ER + breast cancer, further corroborating the link between inadequate vascularity and hypoxia in ER + breast cancer. KEY POINTS: • Hypoxia, measured by [18F]-FMISO-PET, was associated with low microvessel density and small vessel diameters, corroborating the link between inadequate vascularity and hypoxia in ER + breast cancer. • Increased CAIX expression was associated with higher levels of hypoxia measured by [18F]-FMISO-PET. • Morphologic and functional abnormalities of the tumour microvasculature are the major determinants of hypoxia in cancers and support the previously reported perfusion-driven character of hypoxia in breast carcinomas.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.

Deuterium metabolic imaging and hyperpolarized 13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism.

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

Hypoxia and perfusion in breast cancer: simultaneous assessment using PET/MR imaging.

OBJECTIVES: Hypoxia is associated with poor prognosis and treatment resistance in breast cancer. However, the temporally variant nature of hypoxia can complicate interpretation of imaging findings. We explored the relationship between hypoxia and vascular function in breast tumours through combined 18F-fluoromisonidazole (18 F-FMISO) PET/MRI, with simultaneous assessment circumventing the effect of temporal variation in hypoxia and perfusion. METHODS: Women with histologically confirmed, primary breast cancer underwent a simultaneous 18F-FMISO-PET/MR examination. Tumour hypoxia was assessed using influx rate constant Ki and hypoxic fractions (%HF), while parameters of vascular function (Ktrans, kep, ve, vp) and cellularity (ADC) were derived from dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI, respectively. Additional correlates included histological subtype, grade and size. Relationships between imaging variables were assessed using Pearson correlation (r). RESULTS: Twenty-nine women with 32 lesions were assessed. Hypoxic fractions > 1% were observed in 6/32 (19%) cancers, while 18/32 (56%) tumours showed a %HF of zero. The presence of hypoxia in lesions was independent of histological subtype or grade. Mean tumour Ktrans correlated negatively with Ki (r = - 0.38, p = 0.04) and %HF (r = - 0.33, p = 0.04), though parametric maps exhibited intratumoural heterogeneity with hypoxic regions colocalising with both hypo- and hyperperfused areas. No correlation was observed between ADC and DCE-MRI or PET parameters. %HF correlated positively with lesion size (r = 0.63, p = 0.001). CONCLUSION: Hypoxia measured by 18F-FMISO-PET correlated negatively with Ktrans from DCE-MRI, supporting the hypothesis of perfusion-driven hypoxia in breast cancer. Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that combined assessment may be needed for disease characterisation, which could be achieved using simultaneous multimodality imaging. KEY POINTS: • At the tumour level, hypoxia measured by 18F-FMISO-PET was negatively correlated with perfusion measured by DCE-MRI, which supports the hypothesis of perfusion-driven hypoxia in breast cancer. • No associations were observed between 18F-FMISO-PET parameters and tumour histology or grade, but tumour hypoxic fractions increased with lesion size. • Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that the combined hypoxia-perfusion status of tumours may need to be considered for disease characterisation, which can be achieved via simultaneous multimodality imaging as reported here.

Improving the image quality of DWI in breast cancer: comparison of multi-shot DWI using multiplexed sensitivity encoding to conventional single-shot echo-planar imaging DWI.

OBJECTIVE: To compare diffusion-weighted images (DWI) acquired using single-shot echo-planar imaging (ss-EPI) and multiplexed sensitivity encoding (MUSE) in breast cancer. METHODS: 20 females with pathologically confirmed breast cancer (age 51 ± 12 years) were imaged with ss-EPI-DWI and MUSE-DWI. ADC, normalised ADC (nADC), blur and distortion metrics and qualitative image quality scores were compared. The Crété-Roffet and Mattes mutual information metrics were used to evaluate blurring and distortion, respectively. In a breast phantom, six permutations of MUSE-DWI with varying parallel acceleration factor and number of shots were compared. Differences in ADC and nADC were compared using the coefficient of variation in the phantom and a paired t-test in patients. Differences in blur, distortion and qualitative metrics were analysed using a Wilcoxon signed-rank test. RESULTS: There was a low coefficient of variation (<2%) in ADC between ss-EPI-DWI and all MUSE-DWI permutations acquired using the phantom. 22 malignant and three benign lesions were identified in 20 patients. ADC values measured using MUSE were significantly lower compared to ss-EPI for malignant but not benign lesions (p < 0.001, p = 0.21). nADC values were not significantly different (p = 0.62, p = 0.28). Blurring and distortion improved with number of shots and acceleration factor, and significantly improved with MUSE in patients (p < 0.001, p = 0.002). Qualitatively, image quality improved using MUSE. CONCLUSION: MUSE improves the image quality of breast DWI compared to ss-EPI. ADVANCES IN KNOWLEDGE: MUSE-DWI has superior image quality and reduced blurring and distortion compared to ss-EPI-DWI in breast cancer.

The effect of gadolinium-based contrast agent administration on magnetic resonance fingerprinting-based T1 relaxometry in patients with prostate cancer.

Magnetic resonance fingerprinting (MRF) is a rapidly developing fast quantitative mapping technique able to produce multiple property maps with reduced sensitivity to motion. MRF has shown promise in improving the diagnosis of clinically significant prostate cancer but requires further validation as part of a prostate multiparametric (mp) MRI protocol. mpMRI protocol mandates the inclusion of dynamic contrast enhanced (DCE) imaging, known for its significant T1 shortening effect. MRF could be used to measure both pre- and post-contrast T1 values, but its utility must be assessed. In this proof-of-concept study, we sought to evaluate the variation in MRF T1 measurements post gadolinium-based contrast agent (GBCA) injection and the utility of such T1 measurements to differentiate peripheral and transition zone tumours from normal prostatic tissue. We found that the T1 variation in all tissues increased considerably post-GBCA following the expected significant T1 shortening effect, compromising the ability of MRF T1 to identify transition zone lesions. We, therefore, recommend performing MRF T1 prior to DCE imaging to maintain its benefit for improving detection of both peripheral and transition zone lesions while reducing additional scanning time. Demonstrating the effect of GBCA on MRF T1 relaxometry in patients also paves the way for future clinical studies investigating the added value of post-GBCA MRF in PCa, including its dynamic analysis as in DCE-MRF.

Magnetic resonance fingerprinting of the pancreas at 1.5 T and 3.0 T.

Magnetic resonance imaging of the pancreas is increasingly used as an important diagnostic modality for characterisation of pancreatic lesions. Pancreatic MRI protocols are mostly qualitative due to time constraints and motion sensitivity. MR Fingerprinting is an innovative acquisition technique that provides qualitative data and quantitative parameter maps from a single free-breathing acquisition with the potential to reduce exam times. This work investigates the feasibility of MRF parameter mapping for pancreatic imaging in the presence of free-breathing exam. Sixteen healthy participants were prospectively imaged using MRF framework. Regions-of-interest were drawn in multiple solid organs including the pancreas and T1 and T2 values determined. MRF T1 and T2 mapping was performed successfully in all participants (acquisition time:2.4-3.6 min). Mean pancreatic T1 values were 37-43% lower than those of the muscle, spleen, and kidney at both 1.5 and 3.0 T. For these organs, the mean pancreatic T2 values were nearly 40% at 1.5 T and < 12% at 3.0 T. The feasibility of MRF at 1.5 T and 3 T was demonstrated in the pancreas. By enabling fast and free-breathing quantitation, MRF has the potential to add value during the clinical characterisation and grading of pathological conditions, such as pancreatitis or cancer.

Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1-carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (K trans) and washout parameter (k ep) derived from DCE MRI were compared before and after treatment. Results: Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean K trans (132%) and mean k ep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

Author Correction: Ultra Short Echo Time MRI of Iron-Labelled Mesenchymal Stem Cells in an Ovine Osteochondral Defect Model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ultra Short Echo Time MRI of Iron-Labelled Mesenchymal Stem Cells in an Ovine Osteochondral Defect Model.

Multipotent Mesenchymal Stem/Stromal Cells (MSCs) are widely used in cellular therapy for joint repair. However, the use of MSC therapies is complicated by a lack of understanding of the behaviour of cells and repair within the joint. Current methods of MSC tracking include labelling the cells with Super Paramagnetic Iron Oxide nanoparticles (SPIOs). However, standard acquisition sequences (T2 and T2*) give poor anatomical definition in the presence of SPIOs. To avoid anatomical compromise in the presence of SPIOs, we have investigated the use of Ultra-short Echo Time (UTE) MRI, using a 3D cones acquisition trajectory. This method was used to track SPIO labelled MSC injected into joints containing osteochondral defects in experimental sheep. This study demonstrates that multiple echo times from UTE with 3 T MRI can provide excellent anatomical detail of osteochondral defects and demonstrate similar features to histology. This work also monitors the location of SPIO-labelled cells for regenerative medicine of the knee with MRI, histology, and Prussian blue staining. With these methods, we show that the SPIOs do not hone to the site of defect but instead aggregate in the location of injection, which suggests that any repair mechanism with this disease model must trigger a secondary process.

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.