Accelerated Breast Diffusion-weighted Imaging Using Multiband Sensitivity Encoding with the CAIPIRINHA Method: Clinical Experience at 3 T.

Purpose To examine the clinical value of multiband (MB) sensitivity encoding (SENSE)-accelerated diffusion-weighted imaging (DWI) for breast imaging by performing quantitative and qualitative comparisons with conventional diffusion-weighted echo-planar imaging, or conventional DWI (cDWI). Materials and Methods In this prospective study (ClinicalTrials.gov identifier NCT03607552), women with breast cancer were recruited from July 2018 to July 2019 to undergo additional MB SENSE DWI during clinical 3-T breast MRI examinations. The cDWI and MB SENSE DWI acquisitions were assessed both quantitatively and qualitatively. Regions of interest were defined for tumorous and normal tissue, and the tumor apparent diffusion coefficient (ADC), contrast-to-noise ratio (CNR), and signal index (SI) were calculated for both DWI methods. Three readers independently reviewed the two acquisitions side by side and provided relative image quality scores. Tumor ADC, CNR, and SI measures were compared between cDWI and MB SENSE DWI acquisitions by using a paired t test, and reader preferences were evaluated by using the sign test. Results The study included 38 women (median age, 48 years; range, 28-83 years). Overall agreement was good between cDWI and MB SENSE DWI tumor ADC measures (intraclass correlation coefficient, 0.87 [95% CI: 0.75, 0.94]), and no differences were evident in the ADC (median, 0.93 × 10-3 mm2/sec vs 0.87 ×10-3 mm2/sec; P = .50), CNR (2.2 vs 2.3; P = .17), or SI (9.2 vs 9.2; P = .23) measurements. The image quality of cDWI and MB SENSE DWI acquisitions were considered equal for 51% of images (58 of 114), whereas MB SENSE DWI was preferred more often than cDWI (37% [42 of 114] vs 12% [14 of 114]; P < .001). The preference for MB SENSE DWI was most often attributed to better fat suppression. Conclusion MB SENSE can be used to accelerate breast DWI acquisition times without compromising the image quality or the fidelity of quantitative ADC measurements. Keywords: MR-Diffusion-weighted Imaging, Breast, Comparative Studies, Technology Assessment Clinical trial registration no. NCT03607552 © RSNA, 2022.

Restoring RUNX1 deficiency in RUNX1 familial platelet disorder by inhibiting its degradation.

RUNX1 familial platelet disorder (RUNX1-FPD) is an autosomal dominant disorder caused by a monoallelic mutation of RUNX1, initially resulting in approximately half-normal RUNX1 activity. Clinical features include thrombocytopenia, platelet functional defects, and a predisposition to leukemia. RUNX1 is rapidly degraded through the ubiquitin-proteasome pathway. Moreover, it may autoregulate its expression. A predicted kinetic property of autoregulatory circuits is that transient perturbations of steady-state levels result in continued maintenance of expression at adjusted levels, even after inhibitors of degradation or inducers of transcription are withdrawn, suggesting that transient inhibition of RUNX1 degradation may have prolonged effects. We hypothesized that pharmacological inhibition of RUNX1 protein degradation could normalize RUNX1 protein levels, restore the number of platelets and their function, and potentially delay or prevent malignant transformation. In this study, we evaluated cell lines, induced pluripotent stem cells derived from patients with RUNX1-FPD, RUNX1-FPD primary bone marrow cells, and acute myeloid leukemia blood cells from patients with RUNX1 mutations. The results showed that, in some circumstances, transient expression of exogenous RUNX1 or inhibition of steps leading to RUNX1 ubiquitylation and proteasomal degradation restored RUNX1 levels, thereby advancing megakaryocytic differentiation in vitro. Thus, drugs retarding RUNX1 proteolytic degradation may represent a therapeutic avenue for treating bleeding complications and preventing leukemia in RUNX1-FPD.

Breast Cancer Conspicuity on Computed Versus Acquired High b-Value Diffusion-Weighted MRI.

RATIONALE AND OBJECTIVES: On unenhanced diffusion-weighted imaging (DWI), computing or synthesizing high b-value images from lower b-value acquisitions can enhance breast cancer visibility. This study aimed to evaluate relative lesion conspicuity on computed versus acquired diffusion-weighted images and investigate clinical characteristics influencing optimal b-values. MATERIALS AND METHODS: Women with newly diagnosed breast cancer were prospectively enrolled and underwent 3T breast MRI with DWI. Lesion contrast-to-noise ratio (CNR) was measured across a range of b-values (0-2500 s/mm2) for computed and acquired DWI. Three readers independently compared lesion visibility between computed and acquired DWI and selected the optimal b-value. Computed versus acquired DWI was compared quantitatively based on CNR by paired t-test and qualitatively based on reader preference using a sign test. Optimal b-values by qualitative and quantitative assessment were compared by paired t-test, and associations with clinical characteristics were assessed by Wilcoxon rank sum test. RESULTS: The study included 30 women (median age, 48 years); 28 with invasive carcinoma, 2 DCIS. Lesion CNR was higher on acquired versus computed images (p = 0.018), while lesion visibility by reader assessment was not different (p = 0.36). Optimal b-values selected by readers (mean, b = 1411 ± 383 s/mm2) were slightly higher than those based on peak CNR (b = 1233 ± 463 s/mm2, p = 0.023), and were higher for younger (≤50 years) versus older women (p = 0.002) and dense versus nondense breasts (p = 0.015). CONCLUSION: Lesion CNR on computed high b-value images was slightly reduced versus acquired images, but our study suggests that this did not significantly impact lesion visibility. Computing high b-value images offers extra flexibility to adjust b-value during interpretation.