Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Performance of radiomics models for tumour-infiltrating lymphocyte (TIL) prediction in breast cancer: the role of the dynamic contrast-enhanced (DCE) MRI phase.

OBJECTIVE: To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. MATERIALS AND METHODS: This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. RESULTS: Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. CONCLUSION: The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. KEY POINTS: • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Whole-lesion histogram analysis of the apparent diffusion coefficient: Evaluation of the correlation with subtypes of mucinous breast carcinoma.

PURPOSE: To evaluate the utility of the whole-lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC. MATERIALS AND METHODS: This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC-A (20 cases) and PMBC-B (17 cases) groups. All patients underwent preoperative diffusion-weighted imaging (DWI) at 1.5T and the whole-lesion ADC assessments were generated. Histogram-derived ADC parameters were compared between PMBC vs. MMBC and PMBC-A vs. PMBC-B, and receiver operating characteristic (ROC) curve analysis was used to determine optimal histogram parameters for differentiating these groups. RESULTS: The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25th (P = 0.004), 50th (P = 0.004), 75th (P = 0.006), and 90th percentiles (P = 0.013) and skewness (P = 0.021) than did the MMBC group. The 25th percentile of ADC values achieved the highest area under the curve (AUC) (0.792), with a cutoff value of 1.345 × 10-3 mm2 /s, in distinguishing PMBC and MMBC. The PMBC-A group showed significantly higher ADC values for the mean (P = 0.049), 25th (P = 0.015), and 50th (P = 0.026) percentiles and skewness (P = 0.004) than did the PMBC-B group. The 25th percentile of the ADC cutoff value (1.476 × 10-3 mm2 /s) demonstrated the best AUC (0.837) among the ADC values for distinguishing PMBC-A and PMBC-B. CONCLUSION: Whole-lesion ADC histogram analysis enables comprehensive evaluation of an MBC in its entirety and differentiating subtypes of MBC. Thus, it may be a helpful and supportive tool for conventional MRI. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:391-400.

Nomogram for the prediction of triple-negative breast cancer histological heterogeneity based on multiparameter MRI features: A preliminary study including metaplastic carcinoma and non- metaplastic carcinoma.

Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous disease, and different histological subtypes of TNBC have different clinicopathological features and prognoses. Therefore, this study aimed to establish a nomogram model to predict the histological heterogeneity of TNBC: including Metaplastic Carcinoma (MC) and Non-Metaplastic Carcinoma (NMC). Methods: We evaluated 117 patients who had pathologically confirmed TNBC between November 2016 and December 2020 and collected preoperative multiparameter MRI and clinicopathological data. The patients were randomly assigned to a training set and a validation set at a ratio of 3:1. Based on logistic regression analysis, we established a nomogram model to predict the histopathological subtype of TNBC. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. According to the follow-up information, disease-free survival (DFS) survival curve was estimated using the Kaplan-Meier product-limit method. Results: Of the 117 TNBC patients, 29 patients had TNBC-MC (age range, 29-65 years; median age, 48.0 years), and 88 had TNBC-NMC (age range, 28-88 years; median age, 44.5 years). Multivariate logistic regression analysis demonstrated that lesion type (p = 0.001) and internal enhancement pattern (p = 0.001) were significantly predictive of TNBC subtypes in the training set. The nomogram incorporating these variables showed excellent discrimination power with an AUC of 0.849 (95% CI: 0.750-0.949) in the training set and 0.819 (95% CI: 0.693-0.946) in the validation set. Up to the cutoff date for this analysis, a total of 66 patients were enrolled in the prognostic analysis. Six of 14 TNBC-MC patients experienced recurrence, while 7 of 52 TNBC-NMC patients experienced recurrence. The DFS of the two subtypes was significantly different (p=0.035). Conclusions: In conclusion, we developed a nomogram consisting of lesion type and internal enhancement pattern, which showed good discrimination ability in predicting TNBC-MC and TNBC-NMC.

[Vertigo due to enlarged vestibule with lateral semicircular canal dysplasia: an analysis of clinical characteristics].

OBJECTIVE: To explore the clinical characteristics and possible pathological mechanisms of vertigo due to enlarged vestibule with lateral semicircular canal dysplasia. METHODS: A retrospective review was conducted for 5 cases of peripheral vertigo due to enlarged vestibule with lateral semicircular canal dysplasia. Their characteristics of medical history, precipitating factors, course of vertigo, auditory tests, vestibular tests and imaging examine results were analyzed. RESULTS: The clinical characteristics were as follows. (1) Specifics of medical history: 4 cases suffered delays in gross motor development and potential equilibrium dysfunctions. One case failed to recount an earlier medical history, but could maintain normal hearing and vestibular functions for a long time in adulthood. (2) Most cases could identify the precipitating factors of initial attacks, such as head-bumping, nose-blowing and constipation, etc. resulting in sudden rises of intracranial or abdominal pressures. (3) Paroxysmal vertigo and progressive hearing loss were mimicking Meniere disease or large vestibular aqueduct syndrome. But its course of vertigo was different from those of Meniere disease and large vestibular aqueduct syndrome with regards to hearing levels and audiograms. (4) Some cases had positional vertigo. But the results of Dix-Hallpike and Roll tests were different from benign paroxysmal positioning vertigo (BPPV). (5) The inner ear imaging showed enlarged vestibule with lateral semicircular canal dysplasia. CONCLUSION: The enlarged vestibule with lateral semicircular canal dysplasia is a rare etiology of peripheral vertigo. The history of delays in gross motor development and potential equilibrium dysfunctions in childhood may offer important diagnostic clues. And audiological and vestibular tests, high-resolution computed tomography and magnetic resonance may help to ascertain the diagnosis.

Short-Term Effect of Lumbar Traction on Intervertebral Discs in Patients with Low Back Pain: Correlation between the T2 Value and ODI/VAS Score.

OBJECTIVE: The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. DESIGN: Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. RESULTS: In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction (P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation (r = 0.822, r = 0.793). CONCLUSION: T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients' clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.

Whole Volume Apparent Diffusion Coefficient (ADC) Histogram as a Quantitative Imaging Biomarker to Differentiate Breast Lesions: Correlation with the Ki-67 Proliferation Index.

OBJECTIVES: To evaluate the value of the whole volume apparent diffusion coefficient (ADC) histogram in distinguishing between benign and malignant breast lesions and differentiating different molecular subtypes of breast cancers and to assess the correlation between ADC histogram parameters and Ki-67 expression in breast cancers. METHODS: The institutional review board approved this retrospective study. Between September 2016 and February 2019, 189 patients with 84 benign lesions and 105 breast cancers underwent magnetic resonance imaging (MRI). Volumetric ADC histograms were created by placing regions of interest (ROIs) on the whole lesion. The relationships between the ADC parameters and Ki-67 were analysed using Spearman's correlation analysis. RESULTS: Of the 189 breast lesions included, there were significant differences in patient age (P < 0.001) and lesion size (P = 0.006) between the benign and malignant lesions. The results also demonstrated significant differences in all ADC histogram parameters between benign and malignant lesions (all P < 0.001). The median and mean ADC histogram parameters performed better than the other ADC histogram parameters (AUCs were 0.943 and 0.930, respectively). The receiver operating characteristic (ROC) analysis revealed that the 10th percentile ADC value and entropy could determine the human epidermal growth factor receptor 2 (HER-2) status (both P = 0.001) and estrogen receptor (ER)/progesterone receptor (PR) status (P = 0.020 and P = 0.041, respectively). Among all breast cancer lesions, 35 tumours in the low-proliferation group (Ki - 67 < 14%) and 70 tumours in the high-proliferation group (Ki - 67 ≥ 14) were analysed with ROC curves and correlation analyses. The ROC analysis revealed that entropy and skewness could determine the Ki-67 status (P = 0.007 and P < 0.001, respectively), and there were weak correlations between ADC entropy (r = 0.383) and skewness (r = 0.209) and the Ki-67 index. CONCLUSION: The volumetric ADC histogram could serve as an imaging marker to determine breast lesion characteristics and may be a supplemental method in predicting tumour proliferation in breast cancer.

Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer.

PURPOSE: To assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer. METHODS: In total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29-85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student's t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: A statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029). CONCLUSIONS: Our findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.

Can whole-tumor apparent diffusion coefficient histogram analysis be helpful to evaluate breast phyllode tumor grades?

PURPOSE: To investigate whether whole-tumor apparent diffusion coefficient (ADC) histogram analysis could be helpful to evaluate breast phyllode tumor (PT) grades. MATERIALS AND METHODS: This institutional review board-approved retrospective study included 56 PTs (23 benign lesions, 22 borderline lesions, and 11 malignant lesions) from August 2011 to November 2017. MRI was performed using a 1.5 T MR system equipped with a 4-channel SENSE breast coil. All cases were divided into two groups, benign PT (BPT) and borderline or malignant PT (BMPT). The conventional MR parameters included age, longest diameter, shape, margin, internal enhancement characteristics, cystic component of the tumor, wall of the cystic component, peritumoral edema on T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and T2WI signal intensity, time-signal intensity curve (TIC) patterns and early-stage enhancement ratio (EER). The ADC values were determined in three different types of regions of interest (ROIs), including a circular ROI (ROI-c), single-slice ROI (ROI-s), and whole-tumor ROI (ROI-w). All ADC values were measured twice by Observer A and B (with a 2-week interval). The Ki-67 index was determined, and cases were classified into a "negative group" (Ki-67<14%) and a "positive group" (Ki-67≥14%). SPSS Statistics V21.0 was used for the statistical analyses. RESULTS: Our study included 23 cases of BPT and 33 cases of BMPT (including 22 borderline PTs and 11 malignant PTs). Only 23 patients in BMPT group had Ki-67 results, and 17 of these were positive. Regarding conventional MR features, significant differences were observed in the margin (P = 0.011), cystic component (P<0.001), peritumoral edema on T2WI (P<0.001), and cystic wall (P = 0.011) of the PT between the BPT and BMPT groups. Regarding the ADC value, good intraobserver agreement for ROI-c, ROI-s and ROI-w measurements was obtained. For the three different ROIs, the intraclass correlation coefficient (ICC) values were 0.905 for ROI-c (P > 0.05), 0.965 (P > 0.05) for ROI-s and 0.994 (P > 0.05) for ROI-w. ADC parameter indicated that the figure of ROI-s tended to be higher than the ROI-c and ROI-w, while the ROI-c and ROI-w values were similar. However, no significant difference was found in ADC values between the BPT and BMPT groups for ROI-c, ROI-s and mean ROI-w values and the 10th, 25th, 50th and 75th ROI-w. The areas under the ROC curves for the mean ROI-w and the 10th, 25th, 50th and 75th ROI-w were 0.568, 0.613, 0.567, 0.544, and 0.540, respectively. CONCLUSION: Based on the results obtained in our study, the whole-tumor ADC histogram could not improve differentiation of the breast PT grade, while conventional MR images could provide more meaningful information, so morphological characteristics may be valuable than ADC value, and ADC could be used as a supplemental method to differentiate PT grades.

[Using 1H-MRS to evaluate the effects of warm ischemia reperfusion injury on the regeneration of hepatic cells in orthotopic transplanted livers in rats].

OBJECTIVE: To investigate the prognostic value of proton magnetic resonance spectroscopy (1H-MRS) in the study of warm ischemia reperfusion injury to the regeneration of hepatic cells of the livers following their orthotopic transplantation in rats. METHODS: A rat orthotopic liver transplantation (OLT) model with warm ischemia, the experimental group, was established and the same was done with a control group but without warm ischemia of the livers. They were studied at 6 time points (6 hours, 1, 3, 7, 14, and 30 days after OLT). All rats took axial T1 weighted and T2 weighted imaging scans and 1H MR spectroscopies. RESULTS: The positive rate of proliferating cell nuclear antigen (PCNA) and the mean peak choline/water ratio in the experimental group were significantly higher than those in the control group and the peak choline /water ratio had a positive correlation with the positive rate of PCNA. Serum ALT and AST increased significantly after OLT, especially during the 6 hour to 3day period. The levels of ALT and AST were markedly higher in the experimental group compared to the control group. CONCLUSION: Warm ischemia reperfusion injury of OLT has a significant effect on the regeneration of hepatic cells, and the choline peak of 1H-MRS can be used to evaluate the regeneration of hepatic cells non-invasively.