Purpose: A single-sided NMR instrument was used to investigate the ability of the T 1 relaxation constant to distinguish between regions of low and high mammographic density in human breast tissue.Methods: Measurements were performed on 5 breast slices obtained from 3 women undergoing breast reduction surgery or prophylactic mastectomy.Results: T 1 values measured in regions of high mammographic density in both the full breast slices (T 1 5 170 6 30 ms) and excised regions (T 1 5 160 6 30 ms) were found to be significantly different (P < .001) from those measured in regions of low mammographic density, in which T 1 5 120 6 10 ms was observed both in full slices and excised regions. There was no statistically significant difference between the T 1 values measured in the full breast slices and those measured in the excised regions. Conclusion:The findings suggest that portable NMR may provide a low-cost means of assessing mammographic density in vivo. K E Y W O R D S breast cancer risk, longitudinal spin-relaxation time constant (T 1 ), mammographic density, mammography, portable single-sided NMR | I NT ROD UCTI ONMammographic density (MD), also known as breast density, refers to the degree of radio-opacity of the breast as observed on an X-ray mammogram. Mammographic density is determined by the amount of the radiodense fibroglandular tissue (FGT), as opposed to the radiolucent adipose, or fat, tissue in the breast. In addition to having important implications for the efficacy of mammographic breast cancer risk screening, 1 MD is an independent risk factor for breast cancer, with women in the highest MD quartile having 4 to 6 times the risk of developing breast cancer than those in the lowest 10%, after normalization for body mass index and age. 2,3 Although the mammogram is still the current standard for Magn. Reson. Med. 2018;80:1243-1251.wileyonlinelibrary.com/journal/mrm

Purpose: Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X-ray mammography.High-frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment's success. We present a novel approach to quantification of MD in breast tissue using single-sided portable NMR. Its development was motivated by the low cost of portable-NMR instrumentation, the suitability for measurements in vivo, and the absence of ionizing radiation. Methods: Five breast slices were obtained from three patients undergoing prophylactic mastectomy or breast reduction surgery. Carr-Purcell-Meiboom-Gill (CPMG) relaxation curves were measured from (1) regions of high and low MD (HMD and LMD, respectively) in the full breast slices; (2) the same regions excised from the full slices; and (3) excised samples after H 2 O-D 2 O replacement. T 2 distributions were reconstructed from the CPMG decays using inverse Laplace transform. Results: Two major peaks, identified as fat and water, were consistently observed in the T 2 distributions of HMD regions. The LMD T 2 distributions were dominated by the fat peak. The relative areas of the two peaks exhibited statistically significant (P < .005) differences between HMD and LMD regions, enabling their classification as HMD or LMD. The relative-area distributions exhibited no statistically significant differences between full slices and excised samples. Conclusion: T 2 -based portable-NMR analysis is a novel approach to MD quantification. The ability to quantify tissue composition, combined with the low cost of instrumentation, make this approach promising for clinical applications. 1200 | ALI et AL. K E Y W O R D S breast cancer, mammographic density, NMR-MOUSE, nuclear magnetic resonance, single-sided portable NMR, transverse spin relaxation time constant (T 2 )

Knee injury often triggers post-traumatic osteoarthritis (PTOA) that affects articular cartilage (AC), subchondral bone, meniscus and the synovial membrane. The available treatments for PTOA are largely ineffective due to late diagnosis past the “treatment window”. This study aimed to develop a detailed understanding of the time line of the progression of PTOA in murine models through longitudinal observation of the femorotibial joint from the onset of the disease to the advanced stage. Quantitative magnetic resonance microimaging (µMRI) and histology were used to evaluate PTOA-associated changes in the knee joints of rats subjected to knee meniscectomy. Systematic longitudinal changes in the articular cartilage thickness, cartilage T2 and the T2 of epiphysis within medial condyles of the tibia were all found to be associated with the development of PTOA in the animals. The following pathogenesis cascade was found to precede advanced PTOA: meniscal injury → AC swelling → subchondral bone remodelling → proteoglycan depletion → free water influx → cartilage erosion. Importantly, the imaging protocol used was entirely MRI-based. This protocol is potentially suitable for whole-knee longitudinal, non-invasive assessment of the development of OA. The results of this work will inform the improvement of the imaging methods for early diagnosis of PTOA.

Mammographic density (MD) is a strong independent risk factor for breast cancer. Traditional screening for MD using X-ray mammography involves ionising radiation, which is not suitable for young women, those with previous radiation exposure, or those having undergone a partial mastectomy. Therefore, alternative approaches for MD screening that do not involve ionising radiation will be important as the clinical use of MD increases, and as more frequent MD testing becomes desirable for research purposes. We have previously demonstrated the potential utility of spin relaxation-based, single-sided portable-NMR measurements for the purpose of MD quantification. We present here a more refined analysis by quantifying breast tissue density in excised samples on a continuous scale (0% to 100% fibroglandular tissue content) using micro-CT (CT), and comparing the results to spin-relaxation and diffusion portable-NMR measurements of the same samples. CT analysis of mammary tissues containing high-and low-MD (HMD and LMD, respectively) regions had Hounsfield Unit (HU) histograms with a bimodal pattern, with HMD regions exhibiting significantly higher HU values than LMD regions. Quantitative MD (%HMD) values obtained using CT exhibited an excellent correlation with portable-NMR results, namely longitudinal spin-relaxation time constants (T1) and the relative tissue water content obtained from portable-NMR diffusion measurements (R 2 =0.92, p<0.0001 and R 2 =0.96, p<0.0001, respectively). These findings are consistent with our previous results demonstrating relatively high water content in HMD breast tissue, consistent with the high proportion of fibroglandular tissue, FGT, which in turn contains more abundant water-carrying HSPG proteins. We observed an excellent correlation between the T1 values and diffusion NMR-measured relative tissue water content (R 2 =0.94, p<0.0001). These findings demonstrate, for the first time, the ability of single-sided portable NMR to accurately quantify MD in vitro on a continuous scale. The results also indicate that portable-NMR analysis can assist in the identification of features underpinning MD, namely FGT and adipose tissue content. Future work will involve application of portable NMR to quantifying MD in vivo.

Abstract. The aim of this study was to establish an advanced analytical platform for complex in vivo pathologies. We have developed a software program, QuantitativeT2, for voxel-based real-time quantitative T2 magnetic resonance imaging. We analyzed murine brain tumors to confirm feasibility of our method for neurological conditions. Anesthetized mice (with invasive gliomas, and controls) were imaged on a 9.4 Tesla scanner using a Carr-Purcell-Meiboom-Gill sequence. The multiecho T2 decays from axial brain slices were analyzed using QuantitativeT2. T2 distribution histograms demonstrated substantial characteristic differences between normal and pathological brain tissues. Voxel-based quantitative maps of tissue water fraction (WF) and geometric mean T2 (gmT2) revealed the heterogeneous alterations to water compartmentalization caused by pathology. The numeric distribution of WF and gmT2 indicated the extent of tumor infiltration. Relative evaluations between in vivo scans and ex vivo histology indicated that the T2s between 30 and 150 ms were related to cellular density and the integrity of the extracellular matrix. Overall, QuantitativeT2 has demonstrated significant advancements in qT2 analysis with real-time operation. It is interactive with an intuitive workflow; can analyze data from many MR manufacturers; and is released as open-source code to encourage examination, improvement, and expansion of this method. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.