Assessing Tumour Haemodynamic Heterogeneity and Response to Choline Kinase Inhibition Using Clustered Dynamic Contrast Enhanced MRI Parameters in Rodent Models of Glioblastoma.

To investigate the utility of DCE-MRI derived pharmacokinetic parameters in evaluating tumour haemodynamic heterogeneity and treatment response in rodent models of glioblastoma, imaging was performed on intracranial F98 and GL261 glioblastoma bearing rodents. Clustering of the DCE-MRI-based parametric maps (using Tofts, extended Tofts, shutter speed, two-compartment, and the second generation shutter speed models) was performed using a hierarchical clustering algorithm, resulting in areas with poor fit (reflecting necrosis), low, medium, and high valued pixels representing parameters Ktrans, ve, Kep, vp, τi and Fp. There was a significant increase in the number of necrotic pixels with increasing tumour volume and a significant correlation between ve and tumour volume suggesting increased extracellular volume in larger tumours. In terms of therapeutic response in F98 rat GBMs, a sustained decrease in permeability and perfusion and a reduced cell density was observed during treatment with JAS239 based on Ktrans, Fp and ve as compared to control animals. No significant differences in these parameters were found for the GL261 tumour, indicating that this model may be less sensitive to JAS239 treatment regarding changes in vascular parameters. This study demonstrates that region-based clustered pharmacokinetic parameters derived from DCE-MRI may be useful in assessing tumour haemodynamic heterogeneity with the potential for assessing therapeutic response.

Prediction of distant metastases in patients with squamous cell carcinoma of head and neck using DWI and DCE-MRI.

BACKGROUND: The primary purpose was to evaluate the prognostic potential of diffusion imaging (DWI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in predicting distant metastases in squamous cell carcinoma of head and neck (HNSCC) patients. The secondary aim was to examine differences in DWI and DCE-MRI-derived parameters on the basis of human papilloma virus (HPV) status, differentiation grade, and nodal stage of HNSCC. METHODS: Fifty-six patients underwent pretreatment DWI and DCE-MRI. Patients were divided into groups who subsequently did (n = 12) or did not develop distant metastases (n = 44). Median values of apparent diffusion coefficient (ADC), volume transfer constant (Ktrans ), and mean intracellular water-lifetime (τi ) and volume were computed from metastatic lymph nodes and were compared between two groups. Prognostic utility of HPV status, differentiation grading, and nodal staging was also evaluated both in isolation or in combination with MRI parameters in distinguishing patients with and without distant metastases. Additionally, MRI parameters were compared between two groups based on dichotomous HPV status, differentiation grade, and nodal stage. RESULTS: Lower but not significantly different Ktrans (0.51 ± 0.15 minute-1 vs 0.60 ± 0.05 minute-1 ) and not significantly different τi (0.13 ± 0.03 second vs 0.19 ± 0.02 second) were observed in patients who developed distant metastases than those who did not. Additionally, no significant differences in ADC or volume were found. τi, was the best parameter in discriminating two groups with moderate sensitivity (67%) and specificity (61.4%). Multivariate logistic regression analyses did not improve the overall prognostic performance for combination of all variables. A trend toward higher τi was observed in HPV-positive patients than those with HPV-negative patients. Also, a trend toward higher Ktrans was observed in poorly differentiated HNSCCs than those with moderately differentiated HNSCCs. CONCLUSION: Pretreatment DCE-MRI may be useful in predicting distant metastases in HNSCC.

Dynamic Contrast-Enhanced MRI Evaluation of Pathologic Complete Response in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer After HER2-Targeted Therapy.

RATIONALE AND OBJECTIVES: Pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after HER2-targeted therapy correlates increased disease-free survival and decreased mastectomy rates. The aim of this study was to explore tumor shrinkage patterns and initial tumor enhancement with pCR in HER2-positive breast cancer. MATERIALS AND METHODS: This was an institutional review board-approved retrospective analysis of 51 HER2 positive breast cancer patients with breast MRI both pre- and post-HER2-targeted therapy. Initial enhancement ratio (IER, initial enhancement percentage over baseline at first postcontrast imaging), pattern of tumor shrinkage, and Dynamic contrast enhanced (DCE)-MRI imaging features were assessed. Wilcoxon rank, Spearman correlation, Fisher's exact, and Mann-Whitney tests were used to correlate MRI imaging features with pCR. IER reader agreement was evaluated by intraclass correlation. Binary logistic regression was used to evaluate multivariate associations with pCR. RESULTS: 56.9% (29/51) of patients had pCR at surgery. Concentric tumor shrinkage pattern was associated with pCR (p = 0.001, Area under the curve (AUC) 0.778): accuracy 80.4%, specificity 96.6%, and sensitivity of 59.1%. There was no association with pCR and imaging response as defined by RECIST criteria (p = 0.169), pretreatment IER (Reader 1 (R1) p = 0.665, Reader 2 (R2) p = 0.766), or lesion size (p = 0.69). IER was associated with axillary metastases (R1 p = 0.016, R2 < 0.001) and ki-67 (R1 r = 0.52, p = 0.008, R2 r = -0.44, p = 0.028). CONCLUSION: The shrinkage pattern of HER2-positive tumors after targeted therapy may be associated with pCR. There was no association between IER and pCR. Future studies evaluating the correlation of shrinkage patterns to texture radiomics are of interest.

Diffusional kurtosis imaging for differentiation of additional suspicious lesions on preoperative breast MRI of patients with known breast cancer.

PURPOSE: To investigate the potential of diffusional kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) in the evaluation of additional suspicious lesions at preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. MATERIALS AND METHODS: Fifty-three additional suspicious lesions in 45 patients with breast cancer, which were detected on preoperative breast MRI, were examined with a 3-T MR system. DKI and DWI data were obtained using a spin-echo single-shot echo-planar imaging sequence with b-values of 0, 50, 600, 1000, and 3000 s/mm2. Histogram parameters (mean, standard deviation, minimum, maximum, 10th, 25th, 50th, 75th, 90th percentiles, kurtosis, skewness and entropy) of ADC from DWI and diffusivity (D), kurtosis (K) from DKI were calculated after postprocessing. Parameters were compared between benign vs. ductal carcinoma in situ (DCIS) vs. invasive breast lesions and diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis. Correlation between the mean values of D and K was analyzed according to lesion type. RESULTS: Multiple histogram parameters of D (mean, 25th, 50th percentile, 75th percentile, and entropy) differed between benign and invasive breast lesions (all P < 0.005), but none differed between benign vs. DCIS. D-90th percentile differed between DCIS vs. invasive cancer (P = 0.040). K-10th percentile differed between benign vs. DCIS (P = 0.015). ADC-75th percentile differed between benign vs. invasive cancer and ADC-75th percentile, ADC-90th percentile differed between DCIS vs. invasive cancer, respectively (all P < 0.005). ROC curve analysis showed high specificity for discrimination between benign and invasive cancer. D-mean and K-mean showed strong correlation in benign (rs = -0.813) and invasive lesions (rs = -0.853), but no significant correlation in DCIS. CONCLUSION: DKI may aid in the differentiation of additional suspicious lesions at preoperative breast MRI. Both ADC and DKI may have lower potential in differentiating DCIS from benign lesions.

Along-axon diameter variation and axonal orientation dispersion revealed with 3D electron microscopy: implications for quantifying brain white matter microstructure with histology and diffusion MRI.

Tissue microstructure modeling of diffusion MRI signal is an active research area striving to bridge the gap between macroscopic MRI resolution and cellular-level tissue architecture. Such modeling in neuronal tissue relies on a number of assumptions about the microstructural features of axonal fiber bundles, such as the axonal shape (e.g., perfect cylinders) and the fiber orientation dispersion. However, these assumptions have not yet been validated by sufficiently high-resolution 3-dimensional histology. Here, we reconstructed sequential scanning electron microscopy images in mouse brain corpus callosum, and introduced a random-walker (RaW)-based algorithm to rapidly segment individual intra-axonal spaces and myelin sheaths of myelinated axons. Confirmed by a segmentation based on human annotations initiated with conventional machine-learning-based carving, our semi-automatic algorithm is reliable and less time-consuming. Based on the segmentation, we calculated MRI-relevant estimates of size-related parameters (inner axonal diameter, its distribution, along-axon variation, and myelin g-ratio), and orientation-related parameters (fiber orientation distribution and its rotational invariants; dispersion angle). The reported dispersion angle is consistent with previous 2-dimensional histology studies and diffusion MRI measurements, while the reported diameter exceeds those in other mouse brain studies. Furthermore, we calculated how these quantities would evolve in actual diffusion MRI experiments as a function of diffusion time, thereby providing a coarse-graining window on the microstructure, and showed that the orientation-related metrics have negligible diffusion time-dependence over clinical and pre-clinical diffusion time ranges. However, the MRI-measured inner axonal diameters, dominated by the widest cross sections, effectively decrease with diffusion time by ~ 17% due to the coarse-graining over axonal caliber variations. Furthermore, our 3d measurement showed that there is significant variation of the diameter along the axon. Hence, fiber orientation dispersion estimated from MRI should be relatively stable, while the "apparent" inner axonal diameters are sensitive to experimental settings, and cannot be modeled by perfectly cylindrical axons.

Feasibility analysis of early temporal kinetics as a surrogate marker for breast tumor type, grade, and aggressiveness.

BACKGROUND: Screening breast MRI has been shown to preferentially detect high-grade ductal carcinoma in situ (DCIS) and invasive carcinoma, likely due to increased angiogenesis resulting in early initial uptake of contrast. As interest grows in abbreviated screening breast MRI (AB-MRI), markers of early contrast washin that can predict tumor grade and potential aggressiveness are of clinical interest. PURPOSE: To evaluate the feasibility of using the initial enhancement ratio (IER) as a surrogate marker for tumor grade, hormone receptor status, and prognostic markers, as an initial step to being incorporated into AB-MRI. STUDY TYPE: Retrospective. SUBJECTS: In all, 162 women (mean 55.0 years, range 32.8-87.7 years) with 187 malignancies imaged January 2012-November 2015. FIELD STRENGTH/SEQUENCE: Images were acquired at 3.0T with a T1 -weighted gradient echo fat-suppressed-volume interpolated breath-hold sequence. ASSESSMENT: Subjects underwent dynamic contrast-enhanced breast MRI with a 7-channel breast coil. IER (% signal increase over baseline at the first postcontrast acquisition) was assessed and correlated with background parenchymal enhancement, washout curves, stage, and final pathology. STATISTICAL TESTS: Chi-square test, Spearman rank correlation, Mann-Whitney U-tests, Bland-Altman analysis, and receiver operating characteristic curve analysis. RESULTS: IER was higher for invasive cancer than for DCIS (R1/R2, P < 0.001). IER increased with tumor grade (R1: r = 0.56, P < 0.001, R2: r = 0.50, P < 0.001), as ki-67 increased (R1: r = 0.35, P < 0.001; R2 r = 0.35, P < 0.001), and for node-positive disease (R1/R2, P = 0.001). IER was higher for human epidermal growth factor receptor two-positive and triple negative cancers than for estrogen receptor-positive / progesterone receptor-positive tumors (R1 P < 0.001-0.002; R2 P = 0.0.001-0.011). IER had higher sensitivity (80.6% vs. 75.5%) and specificity (55.8% vs. 48.1%) than washout curves for positive nodes, higher specificity (48.1% vs. 36.5%) and positive predictive value (70.2% vs. 66.7%) for high ki-67, and excellent interobserver agreement (intraclass correlation coefficient = 0.82). DATA CONCLUSION: IER, a measurement of early contrast washin, is associated with higher-grade malignancies and tumor aggressiveness and might be potentially incorporated into an AB-MRI protocol. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1692-1700.

Voxelwise analysis of simultaneously acquired and spatially correlated 18 F-fluorodeoxyglucose (FDG)-PET and intravoxel incoherent motion metrics in breast cancer.

PURPOSE: Diffusion-weighted imaging (DWI) and 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) independently correlate with malignancy in breast cancer, but the relationship between their structural and metabolic metrics is not completely understood. This study spatially correlates diffusion, perfusion, and glucose avidity in breast cancer with simultaneous PET/MR imaging and compares correlations with clinical prognostics. METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, with written informed consent and approval of the institutional review board and using simultaneously acquired FDG-PET and DWI, tissue diffusion (Dt ), and perfusion fraction (fp ) from intravoxel incoherent motion (IVIM) analysis were registered to FDG-PET within 14 locally advanced breast cancers. Lesions were analyzed using 2D histograms and correlation coefficients between Dt , fp , and standardized uptake value (SUV). Correlations were compared with prognostics from biopsy, metastatic burden from whole-body PET, and treatment history. RESULTS: SUV||Dt correlation coefficient significantly distinguished treated (0.11 ± 0.24) from nontreated (-0.33 ± 0.26) patients (P = 0.005). SUV||fp correlations were on average negative for the whole cohort (-0.17 ± 0.13). CONCLUSION: Simultaneously acquired and registered FDG-PET/DWI allowed quantifiable descriptions of breast cancer microenvironments that may provide a framework for monitoring and predicting response to treatment. Magn Reson Med 78:1147-1156, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Comparison of conventional DCE-MRI and a novel golden-angle radial multicoil compressed sensing method for the evaluation of breast lesion conspicuity.

PURPOSE: To compare a novel multicoil compressed sensing technique with flexible temporal resolution, golden-angle radial sparse parallel (GRASP), to conventional fat-suppressed spoiled three-dimensional (3D) gradient-echo (volumetric interpolated breath-hold examination, VIBE) MRI in evaluating the conspicuity of benign and malignant breast lesions. MATERIALS AND METHODS: Between March and August 2015, 121 women (24-84 years; mean, 49.7 years) with 180 biopsy-proven benign and malignant lesions were imaged consecutively at 3.0 Tesla in a dynamic contrast-enhanced (DCE) MRI exam using sagittal T1-weighted fat-suppressed 3D VIBE in this Health Insurance Portability and Accountability Act-compliant, retrospective study. Subjects underwent MRI-guided breast biopsy (mean, 13 days [1-95 days]) using GRASP DCE-MRI, a fat-suppressed radial "stack-of-stars" 3D FLASH sequence with golden-angle ordering. Three readers independently evaluated breast lesions on both sequences. Statistical analysis included mixed models with generalized estimating equations, kappa-weighted coefficients and Fisher's exact test. RESULTS: All lesions demonstrated good conspicuity on VIBE and GRASP sequences (4.28 ± 0.81 versus 3.65 ± 1.22), with no significant difference in lesion detection (P = 0.248). VIBE had slightly higher lesion conspicuity than GRASP for all lesions, with VIBE 12.6% (0.63/5.0) more conspicuous (P < 0.001). Masses and nonmass enhancement (NME) were more conspicuous on VIBE (P < 0.001), with a larger difference for NME (14.2% versus 9.4% more conspicuous). Malignant lesions were more conspicuous than benign lesions (P < 0.001) on both sequences. CONCLUSION: GRASP DCE-MRI, a multicoil compressed sensing technique with high spatial resolution and flexible temporal resolution, has near-comparable performance to conventional VIBE imaging for breast lesion evaluation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1746-1752.

Stimulated echo diffusion tensor imaging (STEAM-DTI) with varying diffusion times as a probe of breast tissue.

PURPOSE: To explore the application of diffusion tensor imaging (DTI) for breast tissue and breast pathologies using a stimulated-echo acquisition mode (STEAM) with variable diffusion times. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant study, approved by the local institutional review board, eight patients and six healthy volunteers underwent an MRI examination at 3 Tesla including STEAM-DTI with several diffusion times ranging from 68.5 to 902.5 ms. A DTI model was fitted to the data for each diffusion time, and parametric maps of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for healthy fibroglandular tissue (FGT) and lesions. The median value of radial diffusivity for FGT was fitted to a linear decay to obtain an estimation of the surface-to-volume ratio, from which the radial diameter was calculated. RESULTS: For healthy FGT, radial diffusivity presented a linear decay with the square root of the diffusion time resulting in a range of estimated radial diameters from 202 to 496 µm, while axial diffusivity presented a nearly time-independent diffusion. Residual fat signal was reduced at longer diffusion times due to the shorter T1 of fat. Residual fat signal to the overall signal in the healthy volunteers' FGT was found to range from 2.39% to 2.55% (shortest mixing time), and from 0.40% to 0.51% (longest mixing time) for the b500 images. CONCLUSION: The use of variable diffusion times may provide an in vivo noninvasive tool to probe diffusion lengths in breast tissue and breast pathology, and might aid by improving fat suppression at longer diffusion times. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:84-93.

Evaluation of Breast Lipid Composition in Patients with Benign Tissue and Cancer by Using Multiple Gradient-Echo MR Imaging.

Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 ± 0.06 vs 0.46 ± 0.10; P < .05) and SFA was higher (0.31 ± 0.07 vs 0.19 ± 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 ± 0.06 vs 0.27 ± 0.05; P < .01) and lower SFA (0.19 ± 0.11 vs 0.30 ± 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (©) RSNA, 2016 Online supplemental material is available for this article.

Intravoxel incoherent motion diffusion-weighted MR imaging of breast cancer: association with histopathological features and subtypes.

OBJECTIVE: To evaluate the associations between intravoxel incoherent motion (IVIM)-derived parameters and histopathological features and subtypes of breast cancer. METHODS: Pre-operative MRI from 275 patients with unilateral breast cancer was analyzed. The apparent diffusion coefficient (ADC) and IVIM parameters [tissue diffusion coefficient (Dt), perfusion fraction (fp) and pseudodiffusion coefficient] were obtained from cancer and normal tissue using diffusion-weighted imaging with b-values of 0, 30, 70, 100, 150, 200, 300, 400, 500 and 800 s mm(-2). We then compared the IVIM parameters of tumours with different histopathological features and subtypes. RESULTS: The ADC and Dt were lower and fp was higher in cancers than in normal tissues (p < 0.001). The Dt was lower in high Ki-67 cancer than in low Ki-67 cancer (p = 0.019), whereas ADC showed no significant difference (p = 0.309). Luminal B [human epidermal growth factor receptor 2 (HER2)-negative] cancer showed lower ADC (p = 0.003) and Dt (p = 0.001) than other types. CONCLUSION: We found low tissue diffusivity in high Ki-67 cancer and luminal B (HER2-negative) cancer using IVIM imaging. ADVANCES IN KNOWLEDGE: Low tissue diffusivity is more clearly shown in high Ki-67 tumours and luminal B (HER2-negative) tumours with the IVIM model.

Comparison of Whole-Body (18)F FDG PET/MR Imaging and Whole-Body (18)F FDG PET/CT in Terms of Lesion Detection and Radiation Dose in Patients with Breast Cancer.

Purpose To compare fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and magnetic resonance (MR) imaging with (18)F FDG combined PET and computed tomography (CT) in terms of organ-specific metastatic lesion detection and radiation dose in patients with breast cancer. Materials and Methods From July 2012 to October 2013, this institutional review board-approved HIPAA-compliant prospective study included 51 patients with breast cancer (50 women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who completed PET/MR imaging with diffusion-weighted and contrast material-enhanced sequences after unenhanced PET/CT. Written informed consent for study participation was obtained. Two independent readers for each modality recorded site and number of lesions. Imaging and clinical follow-up, with consensus in two cases, served as the reference standard. Results There were 242 distant metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19 positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of 30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1, seven of eight [88%] for reader 2) metastatic disease at rates similar to those of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3 and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3 and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of 17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%] for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%] for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107 [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed brain metastases in five of 51 (10%) patients. PET/CT trended toward increased sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%] for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P = .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone metastases but not for pulmonary metastases, as compared with that attained with PET/CT, at about half the radiation dose. (©) RSNA, 2016 Online supplemental material is available for this article.

Evaluation of a known breast cancer using an abbreviated breast MRI protocol: Correlation of imaging characteristics and pathology with lesion detection and conspicuity.

OBJECTIVE: This study evaluates use of an abbreviated magnetic resonance imaging protocol with T2-weighted imaging in detecting biopsy-proven unifocal breast cancer. MATERIALS AND METHODS: This is an institutional review board approved retrospective study of patients with biopsy-proven unifocal breast cancer (88% invasive; 12% in situ) undergoing magnetic resonance imaging. In three separate sessions, three breast imagers evaluated (1) T1-weighted non-contrast, post-contrast and post-contrast subtracted images, (2) T1-weighted images with clinical history and prior imaging, and (3) T1-weighted images and T2-weighted images with clinical history and prior imaging. Protocols were compared for cancer detection, reading time and lesion conspicuity. An independent breast radiologist retrospectively analyzed initial enhancement ratio of cancers and retrospectively reviewed lesion morphology and final pathology. RESULTS: All 107 cancers were identified at first protocol by at least one reader; five cancers were missed by either one or two readers. One cancer was missed by one reader at protocols two and three. Mean percentage detection for protocol one was 97.8%; protocol two, 99.4%, protocol three, 99.4%. T2-weighted images did not alter cancer detection but increased lesion conspicuity for 2/3 readers. 3/5 missed lesions were low grade cancers. Initial enhancement ratio was positively associated with increasing tumor grade (p=0.031) and pathology (p=0.002). Reader interpretation time decreased and lesion conspicuity increased as initial enhancement ratio increased. CONCLUSION: Abbreviated magnetic resonance imaging has high rate of detection for known breast cancer and short interpretation time. T2 weighted imaging increased lesion conspicuity without altering detection rate. Initial enhancement ratio correlated with invasive disease and tumor grade.

In vivo quantification of demyelination and recovery using compartment-specific diffusion MRI metrics validated by electron microscopy.

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (ρ=0.66; p=0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (ρ=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PURPOSE: To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. MATERIALS AND METHODS: This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. RESULTS: The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. CONCLUSION: Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. KEY POINTS: • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

Influence of temporal regularization and radial undersampling factor on compressed sensing reconstruction in dynamic contrast enhanced MRI of the breast.

BACKGROUND: To evaluate the influence of temporal sparsity regularization and radial undersampling on compressed sensing reconstruction of dynamic contrast-enhanced (DCE) MRI, using the iterative Golden-angle RAdial Sparse Parallel (iGRASP) MRI technique in the setting of breast cancer evaluation. METHODS: DCE-MRI examinations of the breast (n = 7) were conducted using iGRASP at 3 Tesla. Images were reconstructed with five different radial undersampling schemes corresponding to temporal resolutions between 2 and 13.4 s/frame and with four different weights for temporal sparsity regularization (λ = 0.1, 0.5, 2, and 6 times of noise level). Image similarity to time-averaged reference images was assessed by two breast radiologists and using quantitative metrics. Temporal similarity was measured in terms of wash-in slope and contrast kinetic model parameters. RESULTS: iGRASP images reconstructed with λ = 2 and 5.1 s/frame had significantly (P < 0.05) higher similarity to time-averaged reference images than the images with other reconstruction parameters (mutual information (MI) >5%), in agreement with the assessment of two breast radiologists. Higher undersampling (temporal resolution < 5.1 s/frame) required stronger temporal sparsity regularization (λ ≥ 2) to remove streaking aliasing artifacts (MI > 23% between λ = 2 and 0.5). The difference between the kinetic-model transfer rates of benign and malignant groups decreased as temporal resolution decreased (82% between 2 and 13.4 s/frame). CONCLUSION: This study demonstrates objective spatial and temporal similarity measures can be used to assess the influence of sparsity constraint and undersampling in compressed sensing DCE-MRI and also shows that the iGRASP method provides the flexibility of optimizing these reconstruction parameters in the postprocessing stage using the same acquired data.

Effect of T2* correction on contrast kinetic model analysis using a reference tissue arterial input function at 7 T.

OBJECTIVES: We aimed to investigate the effect of T2* correction on estimation of kinetic parameters from T1-weighted dynamic contrast enhanced (DCE) MRI data when a reference-tissue arterial input function (AIF) is used. MATERIALS AND METHODS: DCE-MRI data were acquired from seven mice with 4T1 mouse mammary tumors using a double gradient echo sequence at 7 T. The AIF was estimated from a region of interest in the muscle. The extended Tofts model was used to estimate pharmacokinetic parameters in the enhancing part of the tumor, with and without T2* correction of the lesion and AIF. The parameters estimated with T2* correction of both the AIF and lesion time-intensity curve were assumed to be the reference standard. RESULTS: For the whole population, there was significant difference (p < 0.05) in transfer constant (K(trans)) between T2* corrected and not corrected methods, but not in interstitial volume fraction (ve). Individually, no significant differences were found in K(trans) and ve of four and six tumors, respectively, between the T2* corrected and not corrected methods. In contrast, K(trans) was significantly underestimated, if the T2* correction was not used, in other tumors for which the median K(trans) was larger than 0.4 min(-1). CONCLUSION: T2* effect on tumors with high K(trans) may not be negligible in kinetic model analysis, even if AIF is estimated from reference tissue where the concentration of contrast agent is relatively low.

Comparison of contrast enhancement and diffusion-weighted magnetic resonance imaging in healthy and cancerous breast tissue.

OBJECTIVE: To measure background parenchymal enhancement (BPE) and compare with other contrast enhancement values and diffusion-weighted MRI parameters in healthy and cancerous breast tissue at the clinical level. MATERIALS AND METHODS: This HIPAA-compliant, IRB approved retrospective study enrolled 77 patients (38 patients with breast cancer - mean age 51.8 ± 10.0 years; 39 high-risk patients for screening evaluation - mean age 46.3 ± 11.7 years), who underwent contrast-enhanced 3T breast MRI. Contrast enhanced MRI and diffusion-weighted imaging were performed to quantify BPE, lesion contrast enhancement, and apparent diffusion coefficient (ADC) metrics in fibroglandular tissue (FGT) and lesions. RESULTS: BPE did not correlate with ADC values. Mean BPE for the lesion-bearing patients was higher (43.9%) compared to that of the high-risk screening patients (28.3%, p=0.004). Significant correlation (r=0.37, p<0.05) was found between BPE and lesion contrast enhancement. CONCLUSION: No significant association was observed between parenchymal or lesion enhancement with conventional apparent diffusion metrics, suggesting that proliferative processes are not co-regulated in cancerous and parenchymal tissue.

Simulation study of the effect of golden-angle KWIC with generalized kinetic model analysis on diagnostic accuracy for lesion discrimination.

PURPOSE: To quantitatively evaluate temporal blurring of dynamic contrast-enhanced MRI data generated using a k-space weighted image contrast (KWIC) image reconstruction technique with golden-angle view-ordering. METHODS: K-space data were simulated using golden-angle view-ordering and reconstructed using a KWIC algorithm with a Fibonacci number of views enforced for each annulus in k-space. Temporal blurring was evaluated by comparing pharmacokinetic model parameters estimated from the simulated data with the true values. Diagnostic accuracy was quantified using receiver operator characteristic curves (ROC) and the area under the ROC curves (AUC). RESULTS: Estimation errors of pharmacokinetic model parameters were dependent on the true curve type and the lesion size. For 10mm benign and malignant lesions, estimated AUC values using the true and estimate AIFs were consistent with the true AUC value. For 5mm benign and 20mm malignant lesions, estimated AUC values using the true and estimated AIFs were 0.906±0.020 and 0.905±0.021, respectively, as compared with the true AUC value of 0.896. CONCLUSIONS: Although the investigated reconstruction algorithm does impose errors in pharmacokinetic model parameter estimation, they are not expected to significantly impact clinical studies of diagnostic accuracy.

Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.

Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PAPERCLIP: