Quantification of breast tissue density: Correlation between single-sided portable NMR and micro-CT measurements.

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 (µCT), and comparing the results to spin-relaxation and diffusion portable-NMR measurements of the same samples. µCT 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 µCT 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 (R2 = 0.92, p < 0.0001 and R2 = 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 (R2 = 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.

Transverse relaxation-based assessment of mammographic density and breast tissue composition by single-sided portable NMR.

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 H2 O-D2 O replacement. T2 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 T2 distributions of HMD regions. The LMD T2 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: T2 -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.

Singlet-assisted diffusion-NMR (SAD-NMR): redefining the limits when measuring tortuosity in porous media.

Long-lived singlet order is exploited in diffusion NMR experiments to successfully measure the tortuosity of randomly packed spheres with diameters ranging from 500 to 1000 µm. The pore spaces in such packings have characteristic length scales well beyond the length scale limit set by spin relaxation in conventional NMR-diffusion experiments. Diffusion times of up to 240 s were used to obtain the restricted diffusion coefficient as a function of diffusion time in the long-time diffusion regime. Experimental results were validated with numerical simulations and data from X-ray micro-computed tomography.

Assessment of collagen fiber orientation dispersion in articular cartilage by small-angle X-ray scattering and diffusion tensor imaging: Preliminary results.

Measurements of the orientational dispersion of collagen fibers in articular cartilage were made using diffusion tensor imaging (DTI) and small-angle X-ray scattering (SAXS) on matched bovine articular cartilage samples. Thirteen pairs of samples were excised from bovine knee joints; each pair was taken from neighboring locations in the same bone. One sample from each pair was used for DTI measurements and the other for SAXS measurements. Fractional anisotropy (FA) values were calculated from the DTI data both for the individual imaging voxels and for whole regions of interest (ROI). The FA values were used as a measure of fiber dispersion and compared to the ellipticities of the fiber orientation distributions obtained from SAXS. Neither the spatially-resolved FA values nor whole-ROI FA values showed any correlation with SAXS ellipticities. We attribute the lack of DTI-SAXS correlation to two principal factors: (1) the significant difference in the imaging resolution of the two techniques; and (2) the inherent limitations of both the SAXS data analysis methodology and the diffusion tensor model in the case of multi-modal fiber orientation distributions. We discuss how these factors could be overcome in future work.

Load-induced changes in the diffusion tensor of ovine anulus fibrosus: A pilot MRI study.

PURPOSE: To assess the feasibility of diffusion tensor imaging (DTI) for evaluating changes in anulus fibrosus (AF) microstructure following uniaxial compression. MATERIALS AND METHODS: Six axially aligned samples of AF were obtained from a merino sheep disc; two each from the anterior, lateral, and posterior regions. The samples were mechanically loaded in axial compression during five cycles at a rate and maximum compressive strain that reflected physiological conditions. DTI was conducted at 7T for each sample before and after mechanical testing. RESULTS: The mechanical response of all samples in unconfined compression was nonlinear. A stiffer response during the first loading cycle, compared to the remaining cycles, was observed. Change in diffusion parameters appeared to be region-dependent. The mean fractional anisotropy increased following mechanical testing. This was smallest in the lateral (2% and 9%) and largest in the anterior and posterior samples (17-25%). The mean average diffusivity remained relatively constant (<2%) after mechanical testing in the lateral and posterior samples, but increased (by 5%) in the anterior samples. The mean angle made by the principal eigenvector with the spine axis in the lateral samples was 73° and remained relatively constant (<2%) following mechanical testing. This angle was smaller in the anterior (55°) and posterior (47°) regions and increased by 6-16° following mechanical testing. CONCLUSION: These preliminary results suggest that axial compression reorients the collagen fibers, such that they become more consistently aligned parallel to the plane of the endplates. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1723-1735.

The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts.

Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution ("maximum ADC") exhibited a strong correlation with the tumour size (r2 = 0.90) and with the inverse of the elastic modulus (r2 = 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours' ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour's response to treatment.

Molecular Dynamics of a Hydrated Collagen Peptide: Insights into Rotational Motion and Residence Times of Single-Water Bridges in Collagen.

Magnetic resonance transverse spin relaxation time constants (T2) of water protons in ordered collagenous tissues are dependent on the orientation of the tissue relative to the static magnetic field. This dependence is commonly referred to as the magic angle (MA) effect and has been attributed to the restricted rotational motion of icelike water bridges in the hydrated triple-helix collagen molecule. Understanding of the molecular mechanism of the MA effect is important for clinical and research applications of magnetic resonance spectroscopy and imaging to tissues, such as articular cartilage, tendons, and ligaments. In this work, we have used molecular dynamics simulations to investigate the subnanosecond time scale dynamics of single-water bridges in a model collagen peptide. We ascertain the residence times and the patterns of restricted rotational motion of water molecules. The key findings are strongly anisotropic rotation patterns of water molecules at bridge sites and a dynamic, rather than icelike, nature of the single-water bridges within the individual triple-helix collagen molecule.