Quantitative US Delta Radiomics to Predict Radiation Response in Individuals with Head and Neck Squamous Cell Carcinoma.

Purpose To investigate the role of quantitative US (QUS) radiomics data obtained after the 1st week of radiation therapy (RT) in predicting treatment response in individuals with head and neck squamous cell carcinoma (HNSCC). Materials and Methods This prospective study included 55 participants (21 with complete response [median age, 65 years {IQR: 47-80 years}, 20 male, one female; and 34 with incomplete response [median age, 59 years {IQR: 39-79 years}, 33 male, one female) with bulky node-positive HNSCC treated with curative-intent RT from January 2015 to October 2019. All participants received 70 Gy of radiation in 33-35 fractions over 6-7 weeks. US radiofrequency data from metastatic lymph nodes were acquired prior to and after 1 week of RT. QUS analysis resulted in five spectral maps from which mean values were extracted. We applied a gray-level co-occurrence matrix technique for textural analysis, leading to 20 QUS texture and 80 texture-derivative parameters. The response 3 months after RT was used as the end point. Model building and evaluation utilized nested leave-one-out cross-validation. Results Five delta (Δ) parameters had statistically significant differences (P < .05). The support vector machines classifier achieved a sensitivity of 71% (15 of 21), a specificity of 76% (26 of 34), a balanced accuracy of 74%, and an area under the receiver operating characteristic curve of 0.77 on the test set. For all the classifiers, the performance improved after the 1st week of treatment. Conclusion A QUS Δ-radiomics model using data obtained after the 1st week of RT from individuals with HNSCC predicted response 3 months after treatment completion with reasonable accuracy. Keywords: Computer-Aided Diagnosis (CAD), Ultrasound, Radiation Therapy/Oncology, Head/Neck, Radiomics, Quantitative US, Radiotherapy, Head and Neck Squamous Cell Carcinoma, Machine Learning Clinicaltrials.gov registration no. NCT03908684 Supplemental material is available for this article. © RSNA, 2024.

Early Changes in Quantitative Ultrasound Imaging Parameters during Neoadjuvant Chemotherapy to Predict Recurrence in Patients with Locally Advanced Breast Cancer.

BACKGROUND: This study was conducted to explore the use of quantitative ultrasound (QUS) in predicting recurrence for patients with locally advanced breast cancer (LABC) early during neoadjuvant chemotherapy (NAC). METHODS: Eighty-three patients with LABC were scanned with 7 MHz ultrasound before starting NAC (week 0) and during treatment (week 4). Spectral parametric maps were generated corresponding to tumor volume. Twenty-four textural features (QUS-Tex1) were determined from parametric maps acquired using grey-level co-occurrence matrices (GLCM) for each patient, which were further processed to generate 64 texture derivatives (QUS-Tex1-Tex2), leading to a total of 95 features from each time point. Analysis was carried out on week 4 data and compared to baseline (week 0) data. ∆Week 4 data was obtained from the difference in QUS parameters, texture features (QUS-Tex1), and texture derivatives (QUS-Tex1-Tex2) of week 4 data and week 0 data. Patients were divided into two groups: recurrence and non-recurrence. Machine learning algorithms using k-nearest neighbor (k-NN) and support vector machines (SVMs) were used to generate radiomic models. Internal validation was undertaken using leave-one patient out cross-validation method. RESULTS: With a median follow up of 69 months (range 7-118 months), 28 patients had disease recurrence. The k-NN classifier was the best performing algorithm at week 4 with sensitivity, specificity, accuracy, and area under curve (AUC) of 87%, 75%, 81%, and 0.83, respectively. The inclusion of texture derivatives (QUS-Tex1-Tex2) in week 4 QUS data analysis led to the improvement of the classifier performances. The AUC increased from 0.70 (0.59 to 0.79, 95% confidence interval) without texture derivatives to 0.83 (0.73 to 0.92) with texture derivatives. The most relevant features separating the two groups were higher-order texture derivatives obtained from scatterer diameter and acoustic concentration-related parametric images. CONCLUSIONS: This is the first study highlighting the utility of QUS radiomics in the prediction of recurrence during the treatment of LABC. It reflects that the ongoing treatment-related changes can predict clinical outcomes with higher accuracy as compared to pretreatment features alone.

Effect of Ultrasound-Stimulated Microbubbles and Hyperthermia on Tumor Vasculature of Breast Cancer Xenograft.

OBJECTIVE: The objective of the present study was to investigate the treatment effects of ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) on breast tumor vasculature. METHODS: Tumor-bearing mice with breast cancer xenografts (MDA-MB-231), were exposed to different treatment conditions consisting of control (no treatment), USMB alone, HT alone, USMB with HT exposures of 10 and 50 minutes. Quantitative 3D Doppler ultrasound and photoacoustic imaging were used to detect tumor blood flow and oxygen saturation, respectively. In addition, histopathological analysis including TUNEL staining for cell death, and CD31 staining for the vessel count, was performed to complement the results of power Doppler and photoacoustic imaging. RESULTS: Results demonstrated a decrease in tumor blood flow as well as oxygenation level following 50 minutes HT treatment either alone or combined with USMB. In contrast, 10 minutes HT alone or combined with USMB had minimal effects on blood flow and tumor oxygenation level. Treatment with HT for 50 minutes caused drops in tumor oxygenation, which were not evident with USMB treatment alone. Additionally, results revealed an increase in cell death after 10 minutes HT with or without USMB and a decrease in vessel count compared to control. Unlike previous studies which demonstrated synergistic treatment effects combining USMB with other modalities such as radiation or chemotherapy, USMB and HT effects were not synergistic in the present study. CONCLUSION: The results here demonstrated HT and USMB both alone or together resulted in a significant reduction in tumor blood flow, tumor oxygenation, and vessel count with observed increases in cell death response.

Radiomics in predicting recurrence for patients with locally advanced breast cancer using quantitative ultrasound.

BACKGROUND: The purpose of the study was to investigate the role of pre-treatment quantitative ultrasound (QUS)-radiomics in predicting recurrence for patients with locally advanced breast cancer (LABC). MATERIALS AND METHODS: A prospective study was conducted in patients with LABC (n = 83). Primary tumours were scanned using a clinical ultrasound device before starting treatment. Ninety-five imaging features were extracted-spectral features, texture, and texture-derivatives. Patients were determined to have recurrence or no recurrence based on clinical outcomes. Machine learning classifiers with k-nearest neighbour (KNN) and support vector machine (SVM) were evaluated for model development using a maximum of 3 features and leave-one-out cross-validation. RESULTS: With a median follow up of 69 months (range 7-118 months), 28 patients had disease recurrence (local or distant). The best classification results were obtained using an SVM classifier with a sensitivity, specificity, accuracy and area under curve of 71%, 87%, 82%, and 0.76, respectively. Using the SVM model for the predicted non-recurrence and recurrence groups, the estimated 5-year recurrence-free survival was 83% and 54% (p = 0.003), and the predicted 5-year overall survival was 85% and 74% (p = 0.083), respectively. CONCLUSIONS: A QUS-radiomics model using higher-order texture derivatives can identify patients with LABC at higher risk of disease recurrence before starting treatment.

Ultrasound delta-radiomics during radiotherapy to predict recurrence in patients with head and neck squamous cell carcinoma.

PURPOSE: This study investigated the use of quantitative ultrasound (QUS) obtained during radical radiotherapy (RT) as a radiomics biomarker for predicting recurrence in patients with node-positive head-neck squamous cell carcinoma (HNSCC). METHODS: Fifty-one patients with HNSCC were treated with RT (70 Gy/33 fractions) (±concurrent chemotherapy) were included. QUS Data acquisition involved scanning an index neck node with a clinical ultrasound device. Radiofrequency data were collected before starting RT, and after weeks 1, and 4. From this data, 31 spectral and related-texture features were determined for each time and delta (difference) features were computed. Patients were categorized into two groups based on clinical outcomes (recurrence or non-recurrence). Three machine learning classifiers were used for the development of a radiomics model. Features were selected using a forward sequential selection method and validated using leave-one-out cross-validation. RESULTS: The median follow up for the entire group was 38 months (range 7-64 months). The disease sites involved neck masses in patients with oropharynx (39), larynx (5), carcinoma unknown primary (5), and hypopharynx carcinoma (2). Concurrent chemotherapy and cetuximab were used in 41 and 1 patient(s), respectively. Recurrence was seen in 17 patients. At week 1 of RT, the support vector machine classifier resulted in the best performance, with accuracy and area under the curve (AUC) of 80% and 0.75, respectively. The accuracy and AUC improved to 82% and 0.81, respectively, at week 4 of treatment. CONCLUSION: QUS Delta-radiomics can predict higher risk of recurrence with reasonable accuracy in HNSCC.Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

Assessment of clinical radiosensitivity in patients with head-neck squamous cell carcinoma from pre-treatment quantitative ultrasound radiomics.

To investigate the role of quantitative ultrasound (QUS) radiomics to predict treatment response in patients with head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy (RT). Five spectral parameters, 20 texture, and 80 texture-derivative features were extracted from the index lymph node before treatment. Response was assessed initially at 3 months with complete responders labelled as early responders (ER). Patients with residual disease were followed to classify them as either late responders (LR) or patients with persistent/progressive disease (PD). Machine learning classifiers with leave-one-out cross-validation was used for the development of a binary response-prediction radiomics model. A total of 59 patients were included in the study (22 ER, 29 LR, and 8 PD). A support vector machine (SVM) classifier led to the best performance with accuracy and area under curve (AUC) of 92% and 0.91, responsively to define the response at 3 months (ER vs. LR/PD). The 2-year recurrence-free survival for predicted-ER, LR, PD using an SVM-model was 91%, 78%, and 27%, respectively (p < 0.01). Pretreatment QUS-radiomics using texture derivatives in HNSCC can predict the response to RT with an accuracy of more than 90% with a strong influence on the survival.Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

A priori prediction of response in multicentre locally advanced breast cancer (LABC) patients using quantitative ultrasound and derivative texture methods.

PURPOSE: We develop a multi-centric response predictive model using QUS spectral parametric imaging and novel texture-derivate methods for determining tumour responses to neoadjuvant chemotherapy (NAC) prior to therapy initiation. MATERIALS AND METHODS: QUS Spectroscopy provided parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average-scatterer-diameter (ASD), and average-acoustic-concentration (AAC) in 78 patients with locally advanced breast cancer (LABC) undergoing NAC. Ultrasound radiofrequency data were collected from Sunnybrook Health Sciences Center (SHSC), University of Texas MD Anderson Cancer Center (MD-ACC), and St. Michaels Hospital (SMH) using two different systems. Texture analysis was used to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS, texture- and texture-derivate parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis for developing a response predictive model to classify responders versus non-responders. Model performance was assessed using leave-one-out cross-validation. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest-neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated. RESULTS: A combination of tumour core and margin classification resulted in a peak response prediction performance of 88% sensitivity, 78% specificity, 84% accuracy, 0.86 AUC, 84% PPV, and 83% NPV, achieved using the SVM-RBF classification algorithm. Other parameters and classifiers performed less well running from 66% to 80% accuracy. CONCLUSIONS: A QUS-based framework and novel texture-derivative method enabled accurate prediction of responses to NAC. Multi-centric response predictive model provides indications of the robustness of the approach to variations due to different ultrasound systems and acquisition parameters.

Quantitative ultrasound radiomics in predicting recurrence for patients with node-positive head-neck squamous cell carcinoma treated with radical radiotherapy.

This prospective study was conducted to investigate the role of quantitative ultrasound (QUS) radiomics in predicting recurrence for patients with node-positive head-neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy (RT). The most prominent cervical lymph node (LN) was scanned with a clinical ultrasound device having central frequency of 6.5 MHz. Ultrasound radiofrequency data were processed to obtain 7 QUS parameters. Color-coded parametric maps were generated based on individual QUS spectral features corresponding to each of the smaller units. A total of 31 (7 primary QUS and 24 texture) features were obtained before treatment. All patients were treated with radical RT and followed according to standard institutional practice. Recurrence (local, regional, or distant) served as an endpoint. Three different machine learning classifiers with a set of maximally three features were used for model development and tested with leave-one-out cross-validation for nonrecurrence and recurrence groups. Fifty-one patients were included, with a median follow up of 38 months (range 7-64 months). Recurrence was observed in 17 patients. The best results were obtained using a k-nearest neighbor (KNN) classifier with a sensitivity, specificity, accuracy, and an area under curve of 76%, 71%, 75%, and 0.74, respectively. All the three features selected for the KNN model were texture features. The KNN-model-predicted 3-year recurrence-free survival was 81% and 40% in the predicted no-recurrence and predicted-recurrence groups, respectively. (p = 0.001). The pilot study demonstrates pretreatment QUS-radiomics can predict the recurrence group with an accuracy of 75% in patients with node-positive HNSCC. Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

Quantitative ultrasound radiomics using texture derivatives in prediction of treatment response to neo-adjuvant chemotherapy for locally advanced breast cancer.

BACKGROUND: To investigate quantitative ultrasound (QUS) based higher-order texture derivatives in predicting the response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). MATERIALS AND METHODS: 100 Patients with LABC were scanned before starting NAC. Five QUS parametric image-types were generated from radio-frequency data over the tumor volume. From each QUS parametric-image, 4 grey level co-occurrence matrix-based texture images were derived (20 QUS-Tex1), which were further processed to create texture derivatives (80 QUS-Tex1-Tex2). Patients were classified into responders and non-responders based on clinical/pathological responses to treatment. Three machine learning algorithms based on linear discriminant (FLD), k-nearest-neighbors (KNN), and support vector machine (SVM) were used for developing radiomic models of response prediction. RESULTS: A KNN-model provided the best results with sensitivity, specificity, accuracy, and area under curve (AUC) of 87%, 81%, 82%, and 0.86, respectively. The most helpful features in separating the two response groups were QUS-Tex1-Tex2 features. The 5-year recurrence-free survival (RFS) calculated for KNN predicted responders and non-responders using QUS-Tex1-Tex2 model were comparable to RFS for the actual response groups. CONCLUSIONS: We report the first study demonstrating QUS texture-derivative methods in predicting NAC responses in LABC, which leads to better results compared to using texture features alone.

Quantitative ultrasound delta-radiomics during radiotherapy for monitoring treatment responses in head and neck malignancies.

AIM: We investigated quantitative ultrasound (QUS) in patients with node-positive head and neck malignancies for monitoring responses to radical radiotherapy (RT). MATERIALS & METHODS: QUS spectral and texture parameters were acquired from metastatic lymph nodes 24 h, 1 and 4 weeks after starting RT. K-nearest neighbor and naive-Bayes machine-learning classifiers were used to build prediction models for each time point. Response was detected after 3 months of RT, and patients were classified into complete and partial responders. RESULTS: Single-feature naive-Bayes classification performed best with a prediction accuracy of 80, 86 and 85% at 24 h, week 1 and 4, respectively. CONCLUSION: QUS-radiomics can predict RT response at 3 months as early as 24 h with reasonable accuracy, which further improves into 1 week of treatment.

Quantitative ultrasound radiomics in predicting response to neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from multi-institutional study.

BACKGROUND: This study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics. METHODS: This was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty-two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co-occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical-pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross-validation was performed using a leave-one-out cross-validation method. RESULTS: Based on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K-nearest neighbors (K-NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%. CONCLUSION: QUS-based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy.

Breast lesion characterization using Quantitative Ultrasound (QUS) and derivative texture methods.

PURPOSE: Accurate and timely diagnosis of breast cancer is extremely important because of its high incidence and high morbidity. Early diagnosis of breast cancer through screening can improve overall prognosis. Currently, biopsy remains as the gold standard for tumor pathological confirmation. Development of diagnostic imaging techniques for rapid and accurate characterization of breast lesions is required. We aim to evaluate the usefulness of texture-derivate features of QUS spectral parametric images for non-invasive characterization of breast lesions. METHODS: QUS Spectroscopy was used to determine parametric images of mid-band fit (MBF), spectral slope (SS), spectral intercept (SI), average scatterer diameter (ASD), and average acoustic concentration (AAC) in 204 patients with suspicious breast lesions. Subsequently, texture analysis techniques were used to generate texture maps from parametric images to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS parameters, texture-parameters and texture-derivate parameters were determined from both tumor core and a 5-mm tumor margin and were used in comparison to histopathological analysis in order to develop a diagnostic model for classifying breast lesions as either benign or malignant. Both leave-one-out and hold-out cross-validations were used to evaluate the performance of the diagnostic model. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated. RESULTS: Core and margin information using the SVM-RBF attained the best classification performance of 90% sensitivity, 92% specificity, 91% accuracy, and 0.93 AUC utilizing QUS parameters and their texture derivatives, evaluated using leave-one-out cross-validation. Implementation of hold-out cross-validation using combination of both core and margin information and SVM-RBF achieved average accuracy and AUC of 88% and 0.92, respectively. CONCLUSIONS: QUS-based framework and derivative texture methods enable accurate classification of breast lesions. Evaluation of the proposed technique on a large cohort using hold-out cross-validation demonstrates its robustness and its generalization.

Quantitative ultrasound radiomics for therapy response monitoring in patients with locally advanced breast cancer: Multi-institutional study results.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with locally advanced breast cancer (LABC). The study was conducted to investigate the utility of quantitative ultrasound (QUS) carried out during NAC to predict the final tumour response in a multi-institutional setting. METHODS: Fifty-nine patients with LABC were enrolled from three institutions in North America (Sunnybrook Health Sciences Centre (Toronto, Canada), MD Anderson Cancer Centre (Texas, USA), and Princess Margaret Cancer Centre (Toronto, Canada)). QUS data were collected before starting NAC and subsequently at weeks 1 and 4 during chemotherapy. Spectral tumour parametric maps were generated, and textural features determined using grey-level co-occurrence matrices. Patients were divided into two groups based on their pathological outcomes following surgery: responders and non-responders. Machine learning algorithms using Fisher's linear discriminant (FLD), K-nearest neighbour (K-NN), and support vector machine (SVM-RBF) were used to generate response classification models. RESULTS: Thirty-six patients were classified as responders and twenty-three as non-responders. Among all the models, SVM-RBF had the highest accuracy of 81% at both weeks 1 and week 4 with area under curve (AUC) values of 0.87 each. The inclusion of week 1 and 4 features led to an improvement of the classifier models, with the accuracy and AUC from baseline features only being 76% and 0.68, respectively. CONCLUSION: QUS data obtained during NAC reflect the ongoing treatment-related changes during chemotherapy and can lead to better classifier performances in predicting the ultimate pathologic response to treatment compared to baseline features alone.

Biophysical features of MagA expression in mammalian cells: implications for MRI contrast.

We compared overexpression of the magnetotactic bacterial gene MagA with the modified mammalian ferritin genes HF + LF, in which both heavy and light subunits lack iron response elements. Whereas both expression systems have been proposed for use in non-invasive, magnetic resonance (MR) reporter gene expression, limited information is available regarding their relative potential for providing gene-based contrast. Measurements of MR relaxation rates in these expression systems are important for optimizing cell detection and specificity, for developing quantification methods, and for refinement of gene-based iron contrast using magnetosome associated genes. We measured the total transverse relaxation rate (R2*), its irreversible and reversible components (R2 and R2', respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells. Clonal lines overexpressing MagA and HF + LF were cultured in the presence and absence of iron supplementation, and mounted in a spherical phantom for relaxation mapping at 3 Tesla. In addition to MR measures, cellular changes in iron and zinc were evaluated by inductively coupled plasma mass spectrometry, in ATP by luciferase bioluminescence and in transferrin receptor by Western blot. Only transverse relaxation rates were significantly higher in iron-supplemented, MagA- and HF + LF-expressing cells compared to non-supplemented cells and the parental control. R2* provided the greatest absolute difference and R2' showed the greatest relative difference, consistent with the notion that R2' may be a more specific indicator of iron-based contrast than R2, as observed in brain tissue. Iron supplementation of MagA- and HF + LF-expressing cells increased the iron/zinc ratio approximately 20-fold, while transferrin receptor expression decreased approximately 10-fold. Level of ATP was similar across all cell types and culture conditions. These results highlight the potential of magnetotactic bacterial gene expression for improving MR contrast.