Histogram analysis of MR quantitative parameters: are they correlated with prognostic factors in prostate cancer?

PURPOSE: To investigate the correlation between quantitative MR parameters and prognostic factors in prostate cancer (PCa). METHOD: A total of 186 patients with pathologically confirmed PCa who underwent preoperative multiparametric MRI (mpMRI), including synthetic MRI (SyMRI), were enrolled from two medical centers. The histogram metrics of SyMRI [T1, T2, proton density (PD)] and apparent diffusion coefficient (ADC) values were extracted. The Mann‒Whitney U test or Student's t test was employed to determine the association between these histogram features and the prognostically relevant factors. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the differentiation performance. Spearman's rank correlation coefficients were calculated to determine the correlations between histogram parameters and the International Society of Urological Pathology (ISUP) grade group as well as pathological T stage. RESULTS: Significant correlations were found between the histogram parameters and the ISUP grade as well as pathological T stage of PCa. Among these histogram parameters, ADC_minimum had the strongest correlation with the ISUP grade (r = - 0.481, p < 0.001), and ADC_Median showed the strongest association with pathological T stage (r = - 0.285, p = 0.008). The ADC_10th percentile exhibited the highest performance in identifying clinically significant prostate cancer (csPCa) (AUC 0.833; 95% CI 0.771-0.883). When discriminating between the status of different prognostically relevant factors, a significant difference was observed between extraprostatic extension-positive and -negative cancers with regard to histogram parameters of the ADC map (10th percentile, 90th percentile, mean, median, minimum) and T1 map (minimum) (p = 0.002-0.032). Moreover, histogram parameters of the ADC map (90th percentile, maximum, mean, median), T2 map (10th percentile, median), and PD map (10th percentile, median) were significantly lower in PCa with perineural invasion (p = 0.009-0.049). The T2 values were significantly lower in patients with seminal vesicle invasion (minimum, p = 0.036) and positive surgical margin (10th percentile, 90th percentile, mean, median, and minimum, p = 0.015-0.025). CONCLUSION: Quantitative histogram parameters derived from synthetic MRI and ADC maps may have great potential for predicting the prognostic features of PCa.

The investigation of reduced field-of-view diffusion-weighted imaging (DWI) in patients with nasopharyngeal carcinoma: comparison with conventional DWI.

BACKGROUND: Field-of-view optimized and constrained undistorted single-shot imaging (FOCUS) is a new sequence that shows enhanced anatomical details, improving the diffusion-weighted (DW) images. PURPOSE: To investigate the value of FOCUS diffusion-weighted imaging (DWI) in the evaluation of nasopharyngeal carcinoma (NPC) and compare it with the single-shot echo planner imaging (SS-EPI) DWI approach. MATERIAL AND METHODS: A total of 87 patients with NPC underwent magnetic resonance imaging, including FOCUS and SS-EPI DWI sequences. The signal-to-noise ratio (SNR), signal-intensity ratio (SIR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values of the nasopharyngeal lesions were measured and compared. According to the clinical stages of patients, T and N were divided into early and advanced stage groups, respectively. The mean ADC values of the two techniques were computed, and the area under the curve (AUC) was estimated to calculate the diagnostic efficiency. RESULTS: Subjective and objective image qualitative values of FOCUS were significantly higher than those of SS-EPI. The ADC values for FOCUS of early T and N stages were significantly lower than those of the advanced stages. CONCLUSION: FOCUS provides significantly better image quality in NPC compared to SS-EPI, with lower ADC values for early-stage disease than late-stage disease.

Quantitative synthetic MRI for predicting locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

OBJECTIVES: To investigate the value of pre-treatment quantitative synthetic MRI (SyMRI) for predicting a good response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. METHODS: This prospective study enrolled 63 patients with locally advanced rectal cancer scheduled to undergo preoperative chemoradiotherapy from January 2019 to June 2021. T1 relaxation time (T1), T2 relaxation time (T2), proton density (PD) from synthetic MRI, and apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) were measured. Independent-sample t-test, the Mann-Whitney U test, the Delong test, and receiver operating characteristic curve (ROC) analyses were used to predict the pathologic complete response (pCR) and T-downstaging. RESULTS: Among the 63 patients, 19 (30%) achieved pCR and 44 (70%) did not, and 24 (38%) achieved T-downstaging, while 44 (62%) did not. The mean T1 and T2 values were significantly lower in the pCR group compared with those in the non-pCR group and in the T-downstage group compared with those in the non-T-downstage group (all p < 0.05). There were no significant differences in the PD and ADC values between the two groups. There were no significant differences between the mean values of T1 and T2 for predicting pCR after CRT (AUC, 0.767 vs. 0.831, p = 0.37). There were no significant differences between the AUC values of T1 and T2 values for the assessment of post-CRT T-downstaging (AUC, 0.746 vs. 0.820, p = 0.506). CONCLUSIONS: In patients with locally advanced rectal cancer, the synthetic MRI-derived T1 relaxation time and T2 relaxation time values are promising imaging markers for predicting a good response to neoadjuvant chemoradiotherapy. KEY POINTS: • Mean T1 and T2 values were significantly lower in the pathologic complete response group and the T-downstage group. • There were no significant differences in the proton density and apparent diffusion coefficient values between the two groups.

Application of synthetic magnetic resonance imaging and DWI for evaluation of prognostic factors in cervical carcinoma: a prospective preliminary study.

OBJECTIVES: To determine the values of quantitative metrics derived from synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in evaluating the prognostic factors of cervical carcinoma (CC). METHODS: In this prospective study, 74 patients with pathologically confirmed CC were enrolled. Pretreatment quantitative metrics including T1, T2 and ADC values were obtained from SyMRI and diffusion-weighted imaging (DWI) sequences. The values of all metrics were compared for different prognostic features using Student's t-test or Mann-Whitney U-test. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were utilized to evaluate the diagnostic performance of quantitative variables. RESULTS: T1 and T2 values of parametrial involvement (PMI)-negative were significantly higher than those of PMI-positive (p = 0.002 and < 0.001), while ADC values did not show a significant difference. The area under curve (AUC) of T1 and T2 values for identifying PMI were 0.743 and 0.831. Only the T2 values showed a significant difference between the lymphovascular space involvement (LVSI)-negative and LVSI-positive (p < 0.001), and the AUC of T2 values for discriminating LVSI was 0.814. The differences of T1, T2, and ADC values between the well/moderately and the poorly differentiated CC were significant (all p < 0.001). The AUCs of T1, T2 and ADC values for predicting differentiation grades were 0.762, 0.830, and 0.808. The combined model of all metrics proved to achieve good diagnostic performance with the AUC of 0.866. CONCLUSION: SyMRI may be a potential noninvasive tool for assessing the prognostic factors such as PMI, LVSI, and differentiation grades in CC. Moreover, the overall diagnostic performances of synthetic quantitative metrics were superior to the ADC values, especially in identifying PMI and LVSI. ADVANCES IN KNOWLEDGE: This is the first study to assess the utility of SyMRI-derived parameters and ADC value in evaluating the prognostic factors in CC.

Diagnostic performance of synthetic magnetic resonance imaging in the prognostic evaluation of rectal cancer.

Background: Numerous factors are related to the prognosis of rectal cancer, including T stage, N stage, metastasis, extramural venous invasion (EMVI), circumferential resection margin (CRM), and tumor differentiation. However, it is still a challenge to precisely evaluate them before therapy; therefore, we investigate whether synthetic magnetic resonance imaging and apparent diffusion coefficient (ADC) values could help predict the prognostic factors of rectal cancer. Methods: Eighty-seven patients (55 men and 32 women; mean age, 59±11 years) with pathologically confirmed rectal cancer were enrolled. Preoperative quantitative metrics, including T1, T2, proton density (PD), and ADC values, were measured with diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and synthetic magnetic resonance imaging acquired by a multi-dynamic multi-echo sequence at 3.0 T, in patients with rectal cancer by two radiologists. We evaluated the diagnostic performance of synthetic magnetic resonance imaging using the independent sample t-test or Mann-Whitney U test and receiver operating characteristic (ROC) curve and multivariate logistic regression analyses and compared the area under the ROC curve of quantitative values using the DeLong test. Results: The T2 and PD values showed a significant reduction among patients with poor differentiation and lymph node metastasis in rectal cancer. The area under the ROC curve values of T2 and PD values for predicting magnetic resonance imaging N stage and differentiation were 0.734, 0.682, and 0.673, 0.686, respectively. Moreover, combining T2 and PD values for magnetic resonance imaging N stage slightly improved the area under the ROC curve value of 0.774 (95% CI, 0.673-0.876). In the present study, the ADC and T1 values were not significant in the differentiation or clinical stage of rectal cancer (RC). Conclusions: Quantitative T2 and PD values obtained by synthetic magnetic resonance imaging might be used for evaluating prognostic factors of rectal cancer noninvasively. Furthermore, combining T2 and PD values further improved the diagnostic performance of magnetic resonance imaging N staging in rectal cancer. The ADC and T1 values were not significant in the differentiation or clinical stage of RC.

Distinguishing benign and malignant lesions on contrast-enhanced breast cone-beam CT with deep learning neural architecture search.

PURPOSE: To utilize a neural architecture search (NAS) approach to develop a convolutional neural network (CNN) method for distinguishing benign and malignant lesions on breast cone-beam CT (BCBCT). METHOD: 165 patients with 114 malignant and 86 benign lesions were collected by two institutions from May 2012 to August 2014. The NAS method autonomously generated a CNN model using one institution's dataset for training (patients/lesions: 71/91) and validation (patients/lesions: 20/23). The model was externally tested on another institution's dataset (patients/lesions: 74/87), and its performance was compared with fine-tuned ResNet-50 models and two breast radiologists who independently read the lesions in the testing dataset without knowing lesion diagnosis. RESULTS: The lesion diameters (mean ± SD) were 18.8 ± 12.9 mm, 22.7 ± 10.5 mm, and 20.0 ± 11.8 mm in the training, validation, and external testing set, respectively. Compared to the best ResNet-50 model, the NAS-generated CNN model performed three times faster and, in the external testing set, achieved a higher (though not statistically different) AUC, with sensitivity (95% CI) and specificity (95% CI) of 0.727, 80% (66-90%), and 60% (42-75%), respectively. Meanwhile, the performances of the NAS-generated CNN and the two radiologists' visual ratings were not statistically different. CONCLUSIONS: Our preliminary results demonstrated that a CNN autonomously generated by NAS performed comparably to pre-trained ResNet models and radiologists in predicting malignant breast lesions on contrast-enhanced BCBCT. In comparison to ResNet, which must be designed by an expert, the NAS approach may be used to automatically generate a deep learning architecture for medical image analysis.

Brain volumetric and fractal analysis of synthetic MRI: A comparative study with conventional 3D T1-weighted images.

PURPOSE: The estimation of brain volumetric measurements based on Synthetic MRI (SyMRI) is easy and fast, however, the consistency of brain volumetric and morphologic measurements based on SyMRI and 3D T1WI should be further addressed. The current study evaluated the impact of spatial resolution on brain volumetric and morphologic measurements using SyMRI, and test whether the brain measurements derived from SyMRI were consistent with those resulted from 3D T1WI. METHOD: Brain volumetric and fractal analysis were applied to thirty healthy subjects, each underwent four SyMRI acquisitions with different spatial resolutions (1 × 1 × 2 mm, 1 × 1x3mm, 1 × 1 × 4 mm, 2 × 2 × 2 mm) and a 3D T1WI (1 × 1 × 1 mm isotropic). The consistency of the SyMRI measurements was tested using one-way non-parametric Kruskal-Wallis test and post hoc Dwass-Steel-Critchlow-Fligner test. The association between SyMRI and 3D T1WI derived measurements was evaluated using linear regression models. RESULTS: Our results demonstrated that both in- and through-plane resolutions show an impact on brain volumetric measurements, while brain parenchymal volume showed high consistency across the SyMRI acquisitions, and high association with the measurements from 3D T1WI. In addition, SyMRI with 1 × 1 × 4 mm resolution showed the strongest association with 3D T1WI compared to other SyMRI acquisitions in both volumetric and fractal analyses. Moreover, substantial differences were found in fractal dimension of both gray and white matter between the SyMRI and 3D T1WI tissue segmentations. CONCLUSIONS: Our results suggested that the measurements from SyMRI with relatively higher in-plane and lower through-plane resolution (1 × 1 × 4 mm) are much closer to 3D T1WI.

The diagnostic performance of quantitative mapping in breast cancer patients: a preliminary study using synthetic MRI.

BACKGROUND: Previous studies have indicated that quantitative MRI (qMR) is beneficial for diagnosis of breast cancer. As a novel qMR technology, synthetic MRI (syMRI) may be advantageous by offering simultaneous generation of T1 and T2 mapping in one scan within a few minutes and without concern to the deposition of the gadolinium contrast agent in cell nucleus. In this study, the potential of quantitative mapping derived from Synthetic MRI (SyMRI) to diagnose breast cancer was investigated. METHODS: From April 2018 to May 2019, a total of 87 patients with suspicious breast lesions underwent both conventional and SyMRI before treatment. The quantitative metrics derived from SyMRI, including T1 and T2 values, were measured in breast lesions. The diagnostic performance of SyMRI was evaluated with unpaired Student's t-tests, receiver operating characteristic curve analysis and multivariate logistic regression analysis. The AUCs of quantitative values were compared using Delong test. RESULTS: Among 77 patients who met the inclusion criteria, 48 were diagnosed with histopathological confirmed breast cancers, and the rest had benign lesions. The breast cancers showed significantly higher T1 (1611.61 ± 215.88 ms) values and lower T2 (80.93 ± 7.51 ms) values than benign lesions. The area under the ROC curve (AUC) values were 0.931 (95% CI: 0.874-0.989) and 0.883 (95% CI: 0.810-0.956) for T1 and T2 maps, respectively, in diagnostic discrimination between breast cancers and benign lesions. A slightly increased AUC of 0.978 (95% CI: 0.915-0.993) was achieved by combining those two relaxation-based quantitative metrics. CONCLUSION: In conclusion, our preliminary study showed that the quantitative T1 and T2 values obtained by SyMRI could distinguish effectively between benign and malignant breast lesions, and T1 relaxation time showed the highest diagnostic efficiency. Furthermore, combining the two quantitative relaxation metrics further improved their diagnostic performance.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Quantitative Differentiation of Breast Tumors: A Meta-Analysis.

Objectives: The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of breast tumors remains debatable among published studies. Therefore, this meta-analysis aimed to pool relevant evidence regarding the diagnostic performance of IVIM-DWI in the differential diagnosis of breast tumors. Methods: Studies on the differential diagnosis of breast lesions using IVIM-DWI were systemically searched in the PubMed, Embase and Web of Science databases in recent 10 years. The standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated using Review Manager 5.3, and Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as assess publication bias and heterogeneity. Fagan's nomogram was used to predict the posttest probabilities. Results: Sixteen studies comprising 1,355 malignant and 362 benign breast lesions were included. Most of these studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer had significant lower ADC (SMD = -1.38, P < 0.001) and D values (SMD = -1.50, P < 0.001), and higher f value (SMD = 0.89, P = 0.001) than benign lesions, except D* value (SMD = -0.30, P = 0.20). Invasive ductal carcinoma showed lower ADC (SMD = 1.34, P = 0.01) and D values (SMD = 1.04, P = 0.001) than ductal carcinoma in situ. D value demonstrated the best diagnostic performance (sensitivity = 86%, specificity = 86%, AUC = 0.91) and highest post-test probability (61, 48, 46, and 34% for D, ADC, f, and D* values) in the differential diagnosis of breast tumors, followed by ADC (sensitivity = 76%, specificity = 79%, AUC = 0.85), f (sensitivity = 80%, specificity = 76%, AUC = 0.85) and D* values (sensitivity = 84%, specificity = 59%, AUC = 0.71). Conclusion: IVIM-DWI parameters are adequate and superior to the ADC in the differentiation of breast tumors. ADC and D values can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. IVIM-DWI is also superior in identifying lymph node metastasis, histologic grade, and hormone receptors, and HER2 and Ki-67 status.

Differentiating the lung lesions using Intravoxel incoherent motion diffusion-weighted imaging: a meta-analysis.

BACKGROUND AND OBJECTIVES: The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of pulmonary tumors remained debatable among published studies. This study aimed to pool and summary the relevant results to provide more robust evidence in this issue using a meta-analysis method. MATERIALS AND METHODS: The researches regarding the differential diagnosis of lung lesions using IVIM-DWI were systemically searched in Pubmed, Embase, Web of science and Wangfang database without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan's nomogram was used to predict the post-test probabilities. RESULTS: Eleven studies with 481 malignant and 258 benign lung lesions were included. Most include studies showed a low to unclear risk of bias and low concerns regarding applicability. Lung cancer demonstrated a significant lower ADC (SMD = -1.17, P < 0.001), D (SMD = -1.02, P < 0.001) and f values (SMD = -0.43, P = 0.005) than benign lesions, except D* value (SMD = 0.01, P = 0.96). D value demonstrated the best diagnostic performance (sensitivity = 89%, specificity = 71%, AUC = 0.90) and highest post-test probability (57, 57, 43 and 43% for D, ADC, f and D* values) in the differential diagnosis of lung tumors, followed by ADC (sensitivity = 85%, specificity = 72%, AUC = 0.86), f (sensitivity = 71%, specificity = 61%, AUC = 0.71) and D* values (sensitivity = 70%, specificity = 60%, AUC = 0.66). CONCLUSION: IVIM-DWI parameters show potentially strong diagnostic capabilities in the differential diagnosis of lung tumors based on the tumor cellularity and perfusion characteristics, and D value demonstrated better diagnostic performance compared to mono-exponential ADC.

Identification and validation of a combined hypoxia and immune index for triple-negative breast cancer.

The interaction between hypoxia and immune status has been confirmed in various cancer settings, and corresponding treatments have been investigated. However, reliable biomarkers are needed for individual treatment, so we sought to develop a novel scoring system based on hypoxia and immune status. Prognostic hypoxia-immune status-related signatures of patients with triple-negative breast cancer (TNBC) were identified in The Cancer Genome Atlas (TCGA) (N = 158), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), and GSE58812 (N = 107). LASSO Cox regression was used for model construction. Hypoxia and immune status expression profiles were analyzed, and infiltrating immune cells were compared. Quantitative real-time PCR (qRT-PCR) was used for validation in the Sun Yat-sen University Cancer Center (SYSUCC) cohort, and immunofluorescence was applied for the detection of hypoxia and immune markers in cancer tissues. Ten cross-cohort prognostic hypoxia-immune signatures were included to construct the comprehensive index of hypoxia and immune (CIHI) in the METABRIC cohort. Two subgroups of patients with distinct hypoxia-immune status conditions were identified using CIHI: hypoxiahigh /immunelow and hypoxialow /immunehigh , with a significantly better overall survival (OS) rate in the latter (P < 0.01). The prognostic value of CIHI was further validated in the TCGA, GSE58812, and SYSUCC cohorts (P < 0.01). Hypoxia-immune signatures were significantly differentially expressed between the two groups, and more active immune responses were observed in the hypoxialow /immunehigh group. Cytotoxic lymphocytes were inversely correlated with CIHI in silico. Differentially expressed CA-IX and stromal PD-L1 were detected between subgroups of the SYSUCC cohort. A hypoxia-immune-based cross-cohort classifier for predicting prognosis was developed and validated, which may guide hypoxia modifier treatment and immunotherapy for TNBC.

Development and validation of a prognostic classifier based on HIF-1 signaling for hepatocellular carcinoma.

HIF-1 (hypoxia-inducible factor 1) signaling played a vital role in HCC (hepatocellular carcinoma) prognosis. We aimed to establish an accurate risk scoring system for HCC prognosis prediction and treatment guidance. 424 samples from TCGA (The Cancer Genome Atlas) and 445 samples from GSE14520 dataset were included as the derivation and validation cohort, respectively. In the derivation cohort, prognostic relevant signatures were selected from sixteen HIF-1 related genes and LASSO regression was adopted for model construction. Tumor-infiltrating immune cells were calculated using CIBERSORT algorithm. HIF-1 signaling significantly increased in HCC samples compared with normal tissues. Scoring system based on SLC2A1, ENO1, LDHA and GAPDH exhibited a continuous predictive ability for OS (overall survival) in HCC patients. PCA and t-SNE analysis confirmed a reliable clustering ability of risk score in both cohorts. Patients were classified into high-risk and low-risk groups and the survival outcomes between the two groups showed significant differences. In the derivation cohort, Cox regression indicated the scoring system was an independent predictor for OS, which was validated in the validation cohort. Different infiltrating immune cells fraction and immune scores were also observed in different groups. Herein, a novel integrated scoring system was developed based on HIF-1 related genes, which would be conducive to the precise treatment of patients.

A Technical Review of Convolutional Neural Network-Based Mammographic Breast Cancer Diagnosis.

This study reviews the technique of convolutional neural network (CNN) applied in a specific field of mammographic breast cancer diagnosis (MBCD). It aims to provide several clues on how to use CNN for related tasks. MBCD is a long-standing problem, and massive computer-aided diagnosis models have been proposed. The models of CNN-based MBCD can be broadly categorized into three groups. One is to design shallow or to modify existing models to decrease the time cost as well as the number of instances for training; another is to make the best use of a pretrained CNN by transfer learning and fine-tuning; the third is to take advantage of CNN models for feature extraction, and the differentiation of malignant lesions from benign ones is fulfilled by using machine learning classifiers. This study enrolls peer-reviewed journal publications and presents technical details and pros and cons of each model. Furthermore, the findings, challenges and limitations are summarized and some clues on the future work are also given. Conclusively, CNN-based MBCD is at its early stage, and there is still a long way ahead in achieving the ultimate goal of using deep learning tools to facilitate clinical practice. This review benefits scientific researchers, industrial engineers, and those who are devoted to intelligent cancer diagnosis.