Transfer learning of pre-treatment quantitative ultrasound multi-parametric images for the prediction of breast cancer response to neoadjuvant chemotherapy.

Locally advanced breast cancer (LABC) is a severe type of cancer with a poor prognosis, despite advancements in therapy. As the disease is often inoperable, current guidelines suggest upfront aggressive neoadjuvant chemotherapy (NAC). Complete pathological response to chemotherapy is linked to improved survival, but conventional clinical assessments like physical exams, mammography, and imaging are limited in detecting early response. Early detection of tissue response can improve complete pathological response and patient survival while reducing exposure to ineffective and potentially harmful treatments. A rapid, cost-effective modality without the need for exogenous contrast agents would be valuable for evaluating neoadjuvant therapy response. Conventional ultrasound provides information about tissue echogenicity, but image comparisons are difficult due to instrument-dependent settings and imaging parameters. Quantitative ultrasound (QUS) overcomes this by using normalized power spectra to calculate quantitative metrics. This study used a novel transfer learning-based approach to predict LABC response to neoadjuvant chemotherapy using QUS imaging at pre-treatment. Using data from 174 patients, QUS parametric images of breast tumors with margins were generated. The ground truth response to therapy for each patient was based on standard clinical and pathological criteria. The Residual Network (ResNet) deep learning architecture was used to extract features from the parametric QUS maps. This was followed by SelectKBest and Synthetic Minority Oversampling (SMOTE) techniques for feature selection and data balancing, respectively. The Support Vector Machine (SVM) algorithm was employed to classify patients into two distinct categories: nonresponders (NR) and responders (RR). Evaluation results on an unseen test set demonstrate that the transfer learning-based approach using spectral slope parametric maps had the best performance in the identification of nonresponders with precision, recall, F1-score, and balanced accuracy of 100, 71, 83, and 86%, respectively. The transfer learning-based approach has many advantages over conventional deep learning methods since it reduces the need for large image datasets for training and shortens the training time. The results of this study demonstrate the potential of transfer learning in predicting LABC response to neoadjuvant chemotherapy before the start of treatment using quantitative ultrasound imaging. Prediction of NAC response before treatment can aid clinicians in customizing ineffectual treatment regimens for individual patients.

Usefulness of computed tomography textural analysis in renal cell carcinoma nuclear grading.

Purpose: To evaluate the usefulness of computed tomography (CT) texture descriptors integrated with machine-learning (ML) models in the identification of clear cell renal cell carcinoma (ccRCC) and for the first time papillary renal cell carcinoma (pRCC) tumor nuclear grades [World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) 1, 2, 3, and 4]. Approach: A total of 143 ccRCC and 21 pRCC patients were analyzed in this study. Texture features were extracted from late arterial phase CT images. A complete separation of training/validation and testing subsets from the beginning to the end of the pipeline was adopted. Feature dimension was reduced by collinearity analysis and Gini impurity-based feature selection. The synthetic minority over-sampling technique was employed for imbalanced datasets. The ML classifiers were logistic regression, SVM, RF, multi-layer perceptron, and K -NN. The differentiation between low grades/ high grades, grade 1/grade 2, grade 3/grade 4, and between all grades was assessed for ccRCC and pRCC datasets. The classification performance was assessed and compared by certain metrics. Results: Textures-based classifiers were able to efficiently identify ccRCC and pRCC grades. An accuracy and area under the characteristic operating curve (AUC) up to 91%/0.9, 91%/0.9, 90%/0.9, and 88%/1 were reached when discriminating ccRCC low grades/ high grades, grade 1/grade 2, grade 3/grade 4, and all grades, respectively. An accuracy and AUC up to 96%/1, 81%/0.8, 86%/0.9, and 88%/0.9 were found when differentiating pRCC low grades/ high grades, grade 1/grade 2, grade 3/grade 4, and all grades, respectively. Conclusion: CT texture-based ML models can be used to assist radiologist in predicting the WHO/ISUP grade of ccRCC and pRCC pre-operatively.

Marmoset brain segmentation from deconvolved magnetic resonance images and estimated label maps.

PURPOSE: The proposed method aims to create label maps that can be used for the segmentation of animal brain MR images without the need of a brain template. This is achieved by performing a joint deconvolution and segmentation of the brain MR images. METHODS: It is based on modeling locally the image statistics using a generalized Gaussian distribution (GGD) and couples the deconvolved image and its corresponding labels map using the GGD-Potts model. Because of the complexity of the resulting Bayesian estimators of the unknown model parameters, a Gibbs sampler is used to generate samples following the desired posterior probability. RESULTS: The performance of the proposed algorithm is assessed on simulated and real MR images by the segmentation of enhanced marmoset brain images into its main compartments using the corresponding label maps created. Quantitative assessment showed that this method presents results that are comparable to those obtained with the classical method-registering the volumes to a brain template. CONCLUSION: The proposed method of using labels as prior information for brain segmentation provides a similar or a slightly better performance compared with the classical reference method based on a dedicated template.

Recent advances in medical image processing for the evaluation of chronic kidney disease.

Assessment of renal function and structure accurately remains essential in the diagnosis and prognosis of Chronic Kidney Disease (CKD). Advanced imaging, including Magnetic Resonance Imaging (MRI), Ultrasound Elastography (UE), Computed Tomography (CT) and scintigraphy (PET, SPECT) offers the opportunity to non-invasively retrieve structural, functional and molecular information that could detect changes in renal tissue properties and functionality. Currently, the ability of artificial intelligence to turn conventional medical imaging into a full-automated diagnostic tool is widely investigated. In addition to the qualitative analysis performed on renal medical imaging, texture analysis was integrated with machine learning techniques as a quantification of renal tissue heterogeneity, providing a promising complementary tool in renal function decline prediction. Interestingly, deep learning holds the ability to be a novel approach of renal function diagnosis. This paper proposes a survey that covers both qualitative and quantitative analysis applied to novel medical imaging techniques to monitor the decline of renal function. First, we summarize the use of different medical imaging modalities to monitor CKD and then, we show the ability of Artificial Intelligence (AI) to guide renal function evaluation from segmentation to disease prediction, discussing how texture analysis and machine learning techniques have emerged in recent clinical researches in order to improve renal dysfunction monitoring and prediction. The paper gives a summary about the role of AI in renal segmentation.

Mean Scatterer Spacing Estimation Using Cepstrum-Based Continuous Wavelet Transform.

The goal of this study was to develop an ultrasound (US) scatterer spacing estimation method using an enhanced cepstral analysis based on continuous wavelet transforms (CWTs). Simulations of backscattering media containing periodic and quasi-periodic scatterers were carried out to test the developed algorithm. Experimental data from HT-29 pellets and in vivo PC3 tumors were then used to estimate the mean scatterer spacing. For simulated media containing quasi-periodic scatterers at 1-mm and 100- [Formula: see text] spacing with 5% positional variation, the developed algorithm yielded a spacing estimation error of ~1% for 25- and 55-MHz US pulses. The mean scatterer spacing of HT-29 cell pellets (31.97 [Formula: see text]) was within 3% of the spacing obtained from histology and agreed with the predicted spacing from simulations based on the same pellets for both frequencies. The agreement extended to in vivo PC3 tumors estimation of the spacing with a variance of 1.68% between the spacing derived from the tumor histology and the application of the CWT to the experimental results. The developed technique outperformed the traditional cepstral methods as it can detect nonprominent peaks from quasi-random scatterer configurations. This work can be potentially used to detect morphological tissue changes during normal development or disease treatment.

Quantitative Ultrasound Imaging for the Differentiation between Fresh and Decellularized Mouse Kidneys.

Decellularization is a technique that permits the removal of cells from intact organs while preserving the extracellular matrix (ECM). It has many applications in various fields such as regenerative medicine and tissue engineering. This study aims to differentiate between fresh and decellularized kidneys using quantitative ultrasound (QUS) parameters. Spectral parameters were extracted from the linear fit of the power spectrum of raw radio frequency data and parametric maps were generated corresponding to the regions of interest, from which four textural parameters were estimated. The results of this study indicated that decellularization affects both spectral and textural parameters. The Mid Band Fit mean and contrast were found to be the best spectral and textural predictors of kidney decellularization, respectively.

Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images.

PURPOSE: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. METHODS: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. RESULTS: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001

Quantitative evaluation of cell death response in vitro and in vivo using conventional-frequency ultrasound.

Previous studies using high-frequency ultrasound have suggested that radiofrequency (RF) spectral analysis can be used to quantify changes in cell morphology to detect cell death response to therapy non-invasively. The study here investigated this at conventional-frequencies, frequently used in clinical settings. Spectral analysis was performed using ultrasound RF data collected with a clinical ultrasound platform. Acute myeloid leukemia (AML-5) cells were exposed to cisplatinum for 0-72 hours in vitro and prepared for ultrasound data collection. Preclinical in vivo experiments were also performed on AML-5 tumour-bearing mice receiving chemotherapy. The mid-band fit (MBF) spectral parameter demonstrated an increase of 4.4 ± 1.5 dBr for in vitro samples assessed 48 hours after treatment, a statistically significant change (p < 0.05) compared to control. Further, in vitro concentration-based analysis of a mixture of apoptotic and untreated cells indicated a mean change of 10.9 ± 2.4 dBr in MBF between 0% and 40% apoptotic cell mixtures. Similar effects were reproduced in vivo with an increase of 4.6 ± 0.3 dBr in MBF compared to control, for tumours with considerable apoptotic areas within histological samples. The alterations in the size of cells and nuclei corresponded well with changes measured in the quantitative ultrasound (QUS) parameters.

Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy.

PURPOSE: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. METHODS: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit to the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. RESULTS: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R(2) of 0.9 was observed when quantified cell death was correlated with changes in midband fit. CONCLUSIONS: Results from QUS analysis presented in this study confirm that acute tumor response is linked to a vascular effect following high doses of radiation therapy. Overall, this is in agreement with previous reports suggesting that acute tumor radiation response is regulated by a vascular-driven response. Data also suggest that Sunitinib may enhance tumor radiosensitivity through a vascular remodeling process, and that QUS may be sensitive to changes in tissue properties associated with vascular remodeling. Finally, the work also demonstrates the ability of QUS methods to monitor response to radiation-based vascular strategies.

Quantitative ultrasound spectroscopic imaging for characterization of disease extent in prostate cancer patients.

Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was investigated clinically for the noninvasive detection and extent characterization of disease in cancer patients and compared to whole-mount, whole-gland histopathology of radical prostatectomy specimens. Fifteen patients with prostate cancer underwent a volumetric transrectal ultrasound scan before radical prostatectomy. Conventional-frequency (~5MHz) ultrasound images and radiofrequency data were collected from patients. Normalized power spectra were used as the basis of quantitative ultrasound spectroscopy. Specifically, color-coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were computed and used to characterize prostate tissue in ultrasound images. Areas of cancer were identified in whole-mount histopathology specimens, and disease extent was correlated to that estimated from quantitative ultrasound parametric images. Midband fit and 0-MHz intercept parameters were found to be best associated with the presence of disease as located on histopathology whole-mount sections. Obtained results indicated a correlation between disease extent estimated noninvasively based on midband fit parametric images and that identified histopathologically on prostatectomy specimens, with an r(2) value of 0.71 (P<.0001). The 0-MHz intercept parameter demonstrated a lower level of correlation with histopathology. Spectral slope parametric maps offered no discrimination of disease. Multiple regression analysis produced a hybrid disease characterization model (r(2)=0.764, P<.05), implying that the midband fit biomarker had the greatest correlation with the histopathologic extent of disease. This work demonstrates that quantitative ultrasound spectroscopic imaging can be used for detecting prostate cancer and characterizing disease extent noninvasively, with corresponding gross three-dimensional histopathologic correlation.

Effect of filtering on the classification rate of nonlinear analysis methods applied to uterine EMG signals.

Nonlinear time series analysis can provide useful information regarding nonlinear features of biological signals. The effect of filtering on the performance of nonlinear methods is not well-understood. In this work, we investigate the effects of signal filtering on the sensitivity of four nonlinear methods: Time reversibility, Sample Entropy, Lyapunov Exponents and Delay Vector Variance. These methods were applied to uterine EMG signals with the aim of using them to discriminate between pregnancy and labor contractions. The signals were filtered using three different band-pass filters before the application of the methods. Results showed that the sensitivity of some methods such as sample entropy was significantly improved with filtering. On the other hand, filtering had little effect on some other methods such as time reversibility. This study concludes that while filtering increases computation time, it may be necessary for some nonlinear methods particularly those with low sensitivity.

Low-frequency quantitative ultrasound imaging of cell death in vivo.

PURPOSE: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models. METHODS: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy. RESULTS: Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r2=0.71, 0.82; p<0.001). CONCLUSIONS: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency, in addition to high-frequency ultrasound, can detect tissue changes associated with cell death in vivo in response to cancer treatments.

Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

BACKGROUND: Conventional frequency quantitative ultrasound in conjunction with textural analysis techniques was investigated to monitor noninvasively the effects of cancer therapies in an in vivo preclinical model. METHODS: Conventional low-frequency (∼7 MHz) and high-frequency (∼20 MHz) ultrasound was used with spectral analysis, coupled with textural analysis on spectral parametric maps, obtained from xenograft tumor-bearing animals (n = 20) treated with chemotherapy to extract noninvasive biomarkers of treatment response. RESULTS: Results indicated statistically significant differences in quantitative ultrasound-based biomarkers in both low- and high-frequency ranges between untreated and treated tumors 12 to 24 hours after treatment. Results of regression analysis indicated a high level of correlation between quantitative ultrasound-based biomarkers and tumor cell death estimates from histologic analysis. Applying textural characterization to the spectral parametric maps resulted in an even stronger correlation (r (2) = 0.97). CONCLUSION: The results obtained in this research demonstrate that quantitative ultrasound at a clinically relevant frequency can monitor tissue changes in vivo in response to cancer treatment administration. Using higher order textural information extracted from quantitative ultrasound spectral parametric maps provides more information at a high sensitivity related to tumor cell death.

Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography.

PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients.

Quantitative ultrasound evaluation of tumor cell death response in locally advanced breast cancer patients receiving chemotherapy.

PURPOSE: Quantitative ultrasound techniques have been recently shown to be capable of detecting cell death through studies conducted on in vitro and in vivo models. This study investigates for the first time the potential of early detection of tumor cell death in response to clinical cancer therapy administration in patients using quantitative ultrasound spectroscopic methods. EXPERIMENTAL DESIGN: Patients (n = 24) with locally advanced breast cancer received neoadjuvant chemotherapy treatments. Ultrasound data were collected before treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Quantitative ultrasound parameters were evaluated for clinically responsive and nonresponding patients. RESULTS: Results indicated that quantitative ultrasound parameters showed significant changes for patients who responded to treatment, and no similar alteration was observed in treatment-refractory patients. Such differences between clinically and pathologically determined responding and nonresponding patients were statistically significant (P < 0.05) after 4 weeks of chemotherapy. Responding patients showed changes in parameters related to cell death with, on average, an increase in mid-band fit and 0-MHz intercept of 9.1 ± 1.2 dBr and 8.9 ± 1.9 dBr, respectively, whereas spectral slope was invariant. Linear discriminant analysis revealed a sensitivity of 100% and a specificity of 83.3% for distinguishing nonresponding patients by the fourth week into a course of chemotherapy lasting several months. CONCLUSION: This study reports for the first time that quantitative ultrasound spectroscopic methods can be applied clinically to evaluate cancer treatment responses noninvasively. The results form a basis for monitoring chemotherapy effects and facilitating the personalization of cancer treatment.

Diffuse optical spectroscopy evaluation of treatment response in women with locally advanced breast cancer receiving neoadjuvant chemotherapy.

The aim of this study was to investigate the potential of diffuse optical spectroscopy for monitoring of patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. Fifteen women receiving treatment for LABC had the affected breast scanned before; 1 week, 4 weeks, and 8 weeks after treatment initiation; and before surgery. Optical properties related to tissue microstructure and biochemical composition were obtained. Clinical and pathologic tumor response was evaluated using whole-mount pathology after mastectomy. Patients who responded to treatment demonstrated an initial increase followed by a drop in optical parameters measured in the whole breast, whereas nonresponding patients demonstrated only a drop in the same parameters 1 week after treatment initiation. Responding patients demonstrated a significant increase of 17% ± 7%, 8% ± 8%, 10% ± 7%, 11% ± 11%, and 16% ± 15% in deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin concentrations, water percentage, and tissue optical index, 1 week after treatment initiation, respectively. In contrast, nonresponding patients had a decrease of 14% ± 9%, 18% ± 7%, 17% ± 7%, 29% ± 7%, and 32% ± 9% in their corresponding optical parameters. Deoxygenated hemoglobin concentration (with 100% sensitivity, 83% specificity) and water percentage (with 75% sensitivity, 100% specificity) were found to be the best predictors of treatment response at 1 week after starting treatment. The results of this study suggest that optical parameters can be potentially used to predict and monitor patients' responses to neoadjuvant chemotherapy and can form a basis for the customization of treatments in which inefficacious treatments can be switched to more efficacious therapies.

Surface modes and acoustic scattering of microspheres and ultrasound contrast agents.

Surface modes of spherical objects subject to ultrasound excitation have been recently proposed to explain experimental measurements of scattering from microspheres and ultrasound contrast agents (UCAs). In this work, the relationship between surface modes and resonance frequencies of microspheres and UCAs is investigated. A finite-element model, built upon the fundamentals of wave propagation and structural mechanics, was introduced and validated against analytical solutions (error <5%). Numerical results showed the existence of a systematic relationship between resonance frequencies and surface modes of a 30 µm microsphere driven at 1-70 MHz. On the contrary, for a 100 nm shelled, 4 µm diameter UCA, no clear relationship between the resonance frequencies and the surface modes was found in the frequency range examined. Instead, the UCA exhibited a collection of complex oscillations, which appear to be a combination of various surface modes and displacements. A study of the effects of varying the shell properties on the backscatter showed the presence of peaks in the backscatter of thick-shelled UCAs, which are not predicted by previous models. In summary, this work presents a systematic effort to examine scattering and surface modes from ultrasound contrast agents using finite-element models.

Quantitative ultrasound visualization of cell death: emerging clinical applications for detection of cancer treatment response.

Differentiable echogeneities exhibited by living and dead cells enables the monitoring of cell death response via quantitative ultrasound techniques at high-frequencies and recently at clinical range frequencies. Such capability can be potentially employed to provide rapid and quantitative functional information in real time, and at the patient bedside for evaluating therapy response early following treatment. This paper summarizes backgrounds on quantitative ultrasound visualization of cell death and highlights its potential capabilities for monitoring cancer treatment response, where favorable results have been reported, according to a recent pilot clinical study.

Quantitative ultrasound spectral parametric maps: early surrogates of cancer treatment response.

Textural characteristics of quantitative ultrasound spectral parametric maps have been proposed for the first time to predict cancer therapy response, early following treatment initiation. Such an early prediction can facilitate personalized medicine in cancer treatment procedures. Patients (n=10) with locally advanced breast cancer received neo-adjuvant chemotherapy, as "up-front" treatment, followed by mastectomy with axillary nodal clearance. Data collection consisted of acquiring tumor ultrasound radio-frequency data prior to neo-adjuvant treatment onset and at 4 times during treatment, in addition to pathological examinations of resected specimens after mastectomy. Several textural features were extracted from parametric maps of mid-band fit and 0-MHz intercept. The relative changes of these features were calculated one week after the treatment commenced, compared to the pre-treatment scan. Statistical analysis performed suggested that five of the applied textural features exhibit statistically significant differences between clinically/pathologically responding and non-responding patients. The promising results obtained represent a substantial step forward towards customizing cancer therapies by using this quantitative imaging modality. This can facilitate the switch of an ineffective treatment for a specific patient to a salvage therapy within weeks, instead of having patient endures months of the ineffective treatment.

Diffuse optical imaging for monitoring treatment response in breast cancer patients.

The necessity for a non-invasive and inexpensive imaging modality to both diagnose and monitor treatment response has lead to renewed interest in the potential of optical imaging. The aim of this study was to investigate the potential of diffuse optical spectroscopy for monitoring of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Fifteen women receiving neoadjuvant treatment for breast cancer had the affected breast scanned 5 times: before, 1 week, 4 weeks, and 8 weeks following initiation of the treatment and prior to surgery. Data was collected using a commercial optical system at four different wavelengths (690 nm, 730 nm, 780 nm, and 830 nm) and used to create three dimensional tomographic images. Mean measured values of deoxyhemoglobin (Hb), oxyhemoglobin (HbO(2)), and water in the entire breast were obtained and integrated over the entire breast volume to calculate the integrated optical index for each parameter. Volume-of-interest weighted tissue Hb, HbO(2), and water corresponding to the tumor were also calculated. Patient response to the treatment was evaluated from clinical and pathological response using whole-mount pathology after mastectomy.