Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

OBJECTIVES: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). METHODS: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). RESULTS: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). CONCLUSIONS: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. CLINICAL RELEVANCE STATEMENT: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. KEY POINTS: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

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.

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

OBJECTIVES: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. METHODS: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. RESULTS: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). CONCLUSIONS: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. KEY POINTS: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

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.

Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study.

Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

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.

Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23Na-MRI.

Sodium MRI (23Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p<0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration.

Relationship between carotid plaque surface morphology and perfusion: a 3D DCE-MRI study.

OBJECTIVE: This study aims to explore the relationship between plaque surface morphology and neovascularization using a high temporal and spatial resolution 4D contrast-enhanced MRI/MRA sequence. MATERIALS AND METHODS: Twenty one patients with either recent symptoms or a carotid artery stenosis ≥40% were recruited in this study. Plaque surface morphology and luminal stenosis were determined from the arterial phase MRA images. Carotid neovascularization was evaluated by a previously validated pharmacokinetic (PK) modeling approach. K trans (transfer constant) and v p (partial plasma volume) were calculated in both the adventitia and plaque. RESULTS: Image acquisition and analysis was successfully performed in 28 arteries. Mean luminal stenosis was 44% (range 11-82%). Both adventitial and plaque K trans in ulcerated/irregular plaques were significantly higher than smooth plaques (0.079 ± 0.018 vs. 0.064 ± 0.011 min-1, p = 0.02; 0.065 ± 0.013 vs. 0.055 ± 0.010 min-1, p = 0.03, respectively). Positive correlations between adventitial K trans and v p against stenosis were observed (r = 0.44, p = 0.02; r = 0.55, p = 0.01, respectively). CONCLUSION: This study demonstrates the feasibility of using a single sequence to acquire both high resolution 4D CE-MRA and DCE-MRI to evaluate both plaque surface morphology and function. The results demonstrate significant relationships between lumen surface morphology and neovascularization.

Non-uniform shrinkage for obtaining computational start shape for in-vivo MRI-based plaque vulnerability assessment.

BACKGROUND: Critical mechanical conditions, such as stress within the structure and shear stress due to blood flow, predicted from in-vivo magnetic resonance image (MRI)-based computational simulations have shown to be potential in assessing carotid plaque vulnerability. Plaque contours obtained from in-vivo MRI are a result of a pressurized configuration due to physiological loading. However, in order to make accurate predictions, the computational model must be based on the loading-free geometry. A shrinkage procedure can be used to obtain the computational start shape. METHOD: In this study, electrocardiograph (ECG)-gated MR-images of carotid plaques were obtained from 28 patients. The contours of each plaque were segmented manually. Additional to a uniform shrinkage procedure, a non-uniform shrinkage refinement procedure was used. This procedure was repeated until the pressurized lumen contour and fibrous cap thickness had the best match with the in-vivo image. RESULTS: Compared to the uniform shrinkage procedure, the non-uniform shrinkage significantly reduced the difference in lumen shape and in cap thickness at the thinnest site. Results indicate that uniform shrinkage would underestimate the critical stress in the structure by 20.5±10.7%. CONCLUSION: For slices with an irregular lumen shape (the ratio of the maximum width to the minimum width is more than 1.05), the non-uniform shrinkage procedure is needed to get an accurate stress profile for mechanics and MRI-based carotid plaque vulnerability assessment.