Applying machine learning classifiers to automate quality assessment of paediatric dynamic susceptibility contrast (DSC-) MRI data.

OBJECTIVE: Investigate the performance of qualitative review (QR) for assessing dynamic susceptibility contrast (DSC-) MRI data quality in paediatric normal brain and develop an automated alternative to QR. METHODS: 1027 signal-time courses were assessed by Reviewer 1 using QR. 243 were additionally assessed by Reviewer 2 and % disagreements and Cohen's κ (κ) were calculated. The signal drop-to-noise ratio (SDNR), root mean square error (RMSE), full width half maximum (FWHM) and percentage signal recovery (PSR) were calculated for the 1027 signal-time courses. Data quality thresholds for each measure were determined using QR results. The measures and QR results trained machine learning classifiers. Sensitivity, specificity, precision, classification error and area under the curve from a receiver operating characteristic curve were calculated for each threshold and classifier. RESULTS: Comparing reviewers gave 7% disagreements and κ = 0.83. Data quality thresholds of: 7.6 for SDNR; 0.019 for RMSE; 3 s and 19 s for FWHM; and 42.9 and 130.4% for PSR were produced. SDNR gave the best sensitivity, specificity, precision, classification error and area under the curve values of 0.86, 0.86, 0.93, 14.2% and 0.83. Random forest was the best machine learning classifier, giving sensitivity, specificity, precision, classification error and area under the curve of 0.94, 0.83, 0.93, 9.3% and 0.89. CONCLUSION: The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification. ADVANCES IN KNOWLEDGE: A new automated quality control method was developed, which trained machine learning classifiers using QR results.

Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.

BACKGROUND: Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. OBJECTIVE: We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types. RESULTS: Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K2=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference. CONCLUSION: Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.

Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.

Brain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols.

Predictors of Satisfying and Impactful Clinical Shadowing Experiences for Underrepresented Minority High School Students Interested in Healthcare Careers.

INTRODUCTION: Diversity among healthcare professionals lags behind the increasing racial and ethnic diversity of the United States' population. Increasing diversity of the health professional workforce may be one strategy to influence healthcare disparities. This study sought to understand factors associated with highly satisfying and impactful clinical shadowing experiences among underrepresented minority (URM) students in a health professional development program for urban high school students. METHODS: We analyzed data from students' summer clinical shadowing experiences in 2016 and 2017. We sought to determine if preceptor factors (e.g. racial and gender concordance with students), or patient related variables (e.g. racial concordance with students, the volume of patients per session) were associated with overall satisfaction with shadowing, the desire to pursue a similar career as their preceptor, and viewing their preceptor as a role model. After each shadowing experience, students completed evaluation forms. Chi-square tests were used for data analysis. RESULTS: Over two summers, 65 high school juniors participated in an average of 14 half-day clinical shadowing sessions; 59 of these students identify as URMs. Among URM students, racial/ethnic concordance between preceptor and student was significantly associated with viewing the preceptor as a role model (p = 0.028). Witnessing a greater number of patient-provider encounters (≥five patients per session) was associated with higher satisfaction with the experience (p = 0.0002), and viewing the preceptor as a role model (p = 0.04). CONCLUSION: To increase diversity of the healthcare workforce, URM students need high volume patient-provider encounters. Racial and/or ethnic concordance of URM students and preceptors may provide for preferable role models.

Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.

The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.

A comparison of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast MRI with and without contrast agent leakage correction in paediatric brain tumours.

OBJECTIVE:: To investigate correlations between MRI perfusion metrics measured by dynamic susceptibility contrast and arterial spin labelling in paediatric brain tumours. METHODS:: 15 paediatric patients with brain tumours were scanned prospectively using pseudo-continuous arterial spin labelling (ASL) and dynamic susceptibility contrast (DSC-) MRI with a pre-bolus to minimise contrast agent leakage. Cerebral blood flow (CBF) maps were produced using ASL. Cerebral blood volume (CBV) maps with and without contrast agent leakage correction using the Boxerman technique and the leakage parameter, K2, were produced from the DSC data. Correlations between the metrics produced were investigated. RESULTS:: Histology resulted in the following diagnoses: pilocytic astrocytoma (n = 7), glioblastoma (n = 1), medulloblastoma (n = 1), rosette-forming glioneuronal tumour of fourth ventricle (n = 1), atypical choroid plexus papilloma (n = 1) and pilomyxoid astrocytoma (n = 1). Three patients had a non-invasive diagnosis of low-grade glioma. DSC CBV maps of T1-enhancing tumours were difficult to interpret without the leakage correction. CBV values obtained with and without leakage correction were significantly different (p < 0.01). A significant positive correlation was observed between ASL CBF and DSC CBV (r = 0.516, p = 0.049) which became stronger when leakage correction was applied (r = 0.728, p = 0.002). K2 values were variable across the group (mean = 0.35, range = -0.49 to 0.64). CONCLUSION:: CBV values from DSC obtained with and without leakage correction were significantly different. Large increases in CBV were observed following leakage correction in highly T1-enhancing tumours. DSC and ASL perfusion metrics were found to correlate significantly in a range of paediatric brain tumours. A stronger relationship between DSC and ASL was seen when leakage correction was applied to the DSC data. Leakage correction should be applied when analysing DSC data in enhancing paediatric brain tumours. ADVANCES IN KNOWLEDGE:: We have shown that leakage correction should be applied when investigating enhancing paediatric brain tumours using DSC-MRI. A stronger correlation was found between CBF derived from ASL and CBV derived from DSC when a leakage correction was employed.

Pre-treatment tumour perfusion parameters and initial RECIST response do not predict long-term survival outcomes for patients with head and neck squamous cell carcinoma treated with induction chemotherapy.

OBJECTIVES: Previously, we showed that pre-treatment tumour plasma perfusion (Fp) predicts RECIST response to induction chemotherapy (ICT) in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or RECIST response post 2 cycles of ICT were prognostic for long-term survival outcomes. METHODS: A prospective study enrolled patients with high stage HNSCC treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed by synchronous cisplatin and intensity modulated radiotherapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and after two cycles of ICT was used to measure Fp and RECIST response. RESULTS: Forty-two patients were recruited and 37 underwent two scans. The median follow-up was 36 (range 23-49) months. Pre-treatment tumour Fp (stratified by median) was not prognostic for overall survival (p = 0.42), disease specific survival (p = 0.20) and locoregional control (p = 0.64). Neither change in tumour Fp nor RECIST response post two cycles of ICT was prognostic for any outcome (p>0.21). CONCLUSION: DCE-MRI parameters do not predict long-term survival outcomes following ICT and RECIST response to ICT may not be an appropriate endpoint to determine early efficacy of a treatment in HNSCC patients.

The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability.

BACKGROUND: The microvascular contrast agent transfer constant Ktrans has shown prognostic value in cervical cancer patients treated with chemoradiotherapy. This study aims to determine whether this is explained by the contribution to Ktrans of plasma flow (Fp), vessel permeability surface-area product (PS), or a combination of both. METHODS: Pre-treatment dynamic contrast-enhanced MRI (DCE-MRI) data from 36 patients were analysed using the two-compartment exchange model. Estimates of Fp, PS, Ktrans, and fractional plasma and interstitial volumes (vp and ve) were made and used in univariate and multivariate survival analyses adjusting for clinicopathologic variables tumour stage, nodal status, histological subtype, patient age, tumour volume, and treatment type (chemoradiotherapy vs radiotherapy alone). RESULTS: In univariate analyses, Fp (HR=0.25, P=0.0095) and Ktrans (HR=0.20, P=0.032) were significantly associated with disease-free survival while PS, vp and ve were not. In multivariate analyses adjusting for clinicopathologic variables, Fp and Ktrans significantly increased the accuracy of survival predictions (P=0.0089). CONCLUSIONS: The prognostic value of Ktrans in cervical cancer patients treated with chemoradiotherapy is explained by microvascular plasma flow (Fp) rather than vessel permeability surface-area product (PS).

Evaluation of intravoxel incoherent motion fitting methods in low-perfused tissue.

PURPOSE: To investigate the robustness of constrained and simultaneous intravoxel incoherent motion (IVIM) fitting methods and the estimated IVIM parameters (D, D* and f) for applications in brain and low-perfused tissues. MATERIALS AND METHODS: Model data simulations relevant to brain and low-perfused tumor tissues were computed to assess the accuracy, relative bias, and reproducibility (CV%) of the fitting methods in estimating the IVIM parameters. The simulations were performed at a series of signal-to-noise ratio (SNR) levels to assess the influence of noise on the fitting. RESULTS: The estimated IVIM parameters from model simulations were found significantly different (P < 0.05) using simultaneous and constrained fitting methods at low SNR. Higher accuracy and reproducibility were achieved with the constrained fitting method. Using this method, the mean error (%) for the estimated IVIM parameters at a clinically relevant SNR = 40 were D 0.35, D* 41.0 and f 4.55 for the tumor model and D 1.87, D* 2.48, and f 7.49 for the gray matter model. The most robust parameters were the IVIM-D and IVIM-f. The IVIM-D* was increasingly overestimated at low perfusion. CONCLUSION: A constrained IVIM fitting method provides more accurate and reproducible IVIM parameters in low-perfused tissue compared with simultaneous fitting. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1325-1334.

Arterial input function and gray matter cerebral blood volume measurements in children.

PURPOSE: To investigate how arterial input functions (AIFs) vary with age in children and compare the use of individual and population AIFs for calculating gray matter CBV values. Quantitative measures of cerebral blood volume (CBV) using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) require measurement of an AIF. AIFs are affected by numerous factors including patient age. Few data presenting AIFs in the pediatric population exists. MATERIALS AND METHODS: Twenty-two previously treated pediatric brain tumor patients (mean age, 6.3 years; range, 2.0-15.3 years) underwent DSC-MRI scans on a 3T MRI scanner over 36 visits. AIFs were measured in the middle cerebral artery. A functional form of an adult population AIF was fitted to each AIF to obtain parameters reflecting AIF shape. The relationship between parameters and age was assessed. Correlations between gray matter CBV values calculated using the resulting population and individual patient AIFs were explored. RESULTS: There was a large variation in individual patient AIFs but correlations between AIF shape and age were observed. The center (r = 0.596, P < 0.001) and width of the first-pass peak (r = 0.441, P = 0.007) were found to correlate significantly with age. Intrapatient coefficients of variation were significantly lower than interpatient values for all parameters (P < 0.001). Differences in CBV values calculated with an overall population and age-specific population AIF compared to those calculated with individual AIFs were 31.3% and 31.0%, respectively. CONCLUSION: Parameters describing AIF shape correlate with patient age in line with expected changes in cardiac output. In pediatric DSC-MRI studies individual patient AIFs are recommended.

Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer.

OBJECTIVES: Non-response to induction chemotherapy (IC) occurs in 30% of head and neck squamous cell carcinoma (HNSCC) and has been predicted by tumor plasma flow (Fp) derived by perfusion computed tomography. The present study was designed to test whether baseline tumor Fp determined by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) would predict IC response. MATERIALS AND METHODS: A prospective open study powered to test the relationship between tumor Fp and response to IC (docetaxel, cisplatin, 5-fluorouracil) enrolled 50 patients with stage IV HNSCC. Response after two IC cycles was measured by MRI using Response Evaluation Criteria in Solid Tumors in 37 patients. Tumor Fp (primary end point) and multiple parameters in tumors and lymph nodes (secondary end points) were generated at baseline. Differences in baseline DCE-MRI parameters according to IC response were assessed by the Mann-Whitney U test, and predictive value by receiver operating characteristic (ROC) analysis. RESULTS: Median baseline tumor Fp was 53.2ml/100ml/min in 25 responders and 23.9 in 12 non-responders (U 82; P=0.027; area under ROC curve (AUC) 0.73). Median baseline Fp in lymph nodes was 25.8ml/100ml/min for 37 nodes in 25 responders and 17.1 for 15 nodes in 12 non-responders (U 186, P=0.066; AUC 0.67). Frequency of IC response in 37 patients was 68% overall, 83% for tumor Fp above the median (40.6ml/100ml/min) and 45% below the median. Other DCE-MRI parameters were not associated with IC response. CONCLUSION: Pre-treatment tumor Fp determined by DCE-MRI predicts IC response in HNSCC.