Background: In spite of antiemetics, postchemotherapy side effects continue to be common and may affect compliance to cancer treatment. Among the known factors associated with increased symptom severity are: younger age, treatment toxicity, expected severity, and distress, but little is still known about the role of other factors. The aim of our study was to investigate the role of individual differences related to sensory perception for posttreatment side effects. Methods: Hundred and twenty-five women receiving adjuvant chemotherapy for breast cancer completed measures of absorption, autonomic perception, somatosensory amplification, trait anxiety, and expected severity at baseline. Pretreatment distress and posttreatment nausea, vomiting, and fatigue were assessed at the 1st, 4th, 6th and last cycles of chemotherapy. Results: While univariate analyses showed several factors to be associated with side effects, only absorption and pretreatment distress remained independent predictors of nausea and fatigue when controlling for the remaining factors. Posttreatment vomiting was only predicted by expected severity of vomiting. Conclusion: Chemotherapy-induced side effects are related to increased autonomic nervous system activity, and absorption has been associated with increased autonomic nervous system reactivity to stress. The results suggest that individuals with high absorption may be at greater risk for developing side effects. Improved precision in identifying patients at risk of experiencing more severe side effects after cancer treatment will increase the ability to target treatments aimed at reducing these side effects.

Purpose:The clinical efficacy of breast elastography may be limited when the authors employ the assumption that soft tissues exhibit linear, frequency-independent isotropic mechanical properties during the recovery of shear modulus. Thus, the purpose of this research was to evaluate the degradation in performance incurred when linear-elastic MR reconstruction methods are applied to phantoms that are fabricated using viscoelastic materials. Methods: To develop phantoms with frequency-dependent mechanical properties, the authors measured the complex modulus of two groups of cylindrical-shaped gelatin samples over a wide frequency range ͑up to 1 kHz͒ with the established principles of time-temperature superposition ͑TTS͒. In one group of samples, the authors added varying amounts of agar ͑1%-4%͒; in the other group, the authors added varying amounts of sucrose ͑2.5%-20%͒. To study how viscosity affected the performance of the linear-elastic reconstruction method, the authors constructed an elastically heterogeneous MR phantom to simulate the case where small viscoelastic lesions were surrounded by relatively nonviscous breast tissue. The breast phantom contained four linear, viscoelastic spherical inclusions ͑10 mm diameter͒ that were embedded in normal gelatin. The authors imaged the breast phantom with a clinical prototype of a MRE system and recovered the shear-modulus distribution using the overlapping-subzone-linear-elastic image-reconstruction method. The authors compared the recovered shear modulus to that measured using the TTS method. Results: The authors demonstrated that viscoelastic phantoms could be fabricated by including sucrose in the gelation process and that small viscoelastic inclusions were visible in MR elastograms recovered using a linear-elastic MR reconstruction process; however, artifacts that degraded contrast and spatial resolution were more prominent in highly viscoelastic inclusions. The authors also established that the accuracy of the MR elastograms depended on the degree of viscosity that the inclusion exhibited. Conclusions:The results demonstrated that reconstructing shear modulus from other constitutive laws, such as viscosity, should improve both the accuracy and quality of MR elastograms of the breast.

Our results partly confirm the results of a previous study showing absorption and autonomic perception as predictors of anticipatory side effects in cancer patients receiving chemotherapy. Individuals high in absorption may be more autonomically reactive to aversive stimuli and, subsequently, more conditionable. Additional radiotherapy could be a competing stimulus, reducing the conditioning of chemotherapy-related nausea. Further studies investigating possible psycho-physiological mechanisms in the development of AN are needed.

Background Imaging technologies monitoring and predicting breast cancer response to neoadjuvant chemotherapy (NAC) are of increasing interest. The utility of conventional imaging approaches varies and identifies the need for alternate functional imaging strategies. The use of model-based photon migration methods to quantitatively separate light absorption from scattering in multiply-scattering tissues is a type of near-infrared spectroscopy (NIRS) broadly referred to as diffuse optical spectroscopy (DOS) [Bevilacqua, et al. Applied Optics, 2000; Jakubowski, et al., J of Applied Optics, 2009]. DOSI is a promising experimental technology that allows patients undergoing NAC to be followed with a “no significant risk” device meeting Food and Drug Administration criteria for exempt status. The current design is a mobile device which offers increased accessibility and is relatively simple to perform and interpret, as compared to mammography, magnetic resonance imaging, and positron emission tomography. Due to its size and portability, DOSI is a low barrier-to-access technology, creating new opportunities for patients to receive personalized treatment and for physicians to gain new insight into response mechanisms. The long-term goal is to provide oncologists with a relatively simple, risk-free bedside tool that can be used to help inform medical decisions on chemotherapy regimen, duration, and timing of surgery, thereby maximizing therapeutic response and minimizing unnecessary toxicity. Trial design: In this phase I/II prospective single arm study, patients will receive SOC NAC at five (5) NCI Network for Translational Research in Optical Imaging (NTROI) clinical sites with identical DOSI instruments and procedures. Patients will receive four DOSI exams: at baseline before chemotherapy, at early therapy 5–10 days after NAC initiation, at mid therapy, and at post therapy prior to surgery. The protocol will evaluate a harmonized DOSI technology platform that has been standardized for NAC monitoring. Eligibility: Women who have been diagnosed with breast cancer, have had confirmation by pre-treatment biopsy, and are scheduled to receive NAC followed by surgery are eligible for this trial. Specific aims: The primary aim of this clinical trial is to determine whether the baseline to mid-therapy changes in the DOSI measurement of the quantitative tumor tissue optical index can predict final pathologic complete response in patients with breast cancer undergoing NAC. The secondary aims investigate the correlation between additional DOSI quantitative measurements of tumor biochemical composition obtained at other timepoints, the full range of pathologic response (i.e. complete, partial, and non-response), and any corresponding imaging measurements. Statistical methods: Logistic regression models will be used to study the relationships between pathological complete response and percent change in tissue optical index tumor to normal ratio at different imaging time points. Study size: A total of sixty (60) patients will be enrolled in this imaging study. Currently, one patient has accrued. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-02.

Image‐guided near infrared spectroscopy (IG‐NIRS) provides deep tissue functional characterization at high resolution. This approach combines conventional imaging techniques such as MRI and CT with optical near infrared technologies, giving information directly relating to the vascular and metabolic status of tissue in‐vivo. The resultant estimates of total hemoglobin, oxygen saturation, water, lipids and scatter provide a window towards understanding the mechanisms of cancer in terms of angiogenesis, hypoxia, changes in the interstitium and cell organelle structural changes. This type of spectroscopy has been applied for breast cancer diagnosis and treatment monitoring, as well as image‐guided fluorescence in small‐animals. Optimization of these systems is essential to provide quantitative and accurate spectroscopy. This optimization encompasses system design for simultaneous multi‐modality image acquisition, methods for intelligently combining spatial anatomical structure from MRI/CT into optical recovery, image segmentation, visualization and interpretation of novel combined optical and MRI/CT parameters. This talk will provide an over‐view of these aspects of multi‐modality imaging as well as results from in‐vivo clinical applications. Learning Objectives: 1. Understanding the rationale for multi‐modality IG‐NIRS systems 2. Understanding the type of information and contrast available through these systems 3. Understanding the challenges towards clinical use of these systems.

Background: NIRST, a noninvasive imaging with no ionizing radiation, has been found to be prognostic as a tool to monitor early pathologic response to NAC in BC using biophysical properties of the tumor compared with normal breast tissue. We aim to establish NIRST indicators as early surrogates of treatment response and to evaluate its potential as a predictive tool in treatment decisions. Methods: 27 women with locally advanced BC undergoing NAC were enrolled in this pilot study. NIRST imaging was performed pre-treatment, after cycle 1 and 2, at the mid-point of NAC, and at the conclusion of NAC prior to surgery. Biophysical data including oxy- and deoxy-hemoglobin, water, lipid, and scatter components were obtained at these time points. To minimize inter-subject variability due to breast density and its effects on the NIRST data, statistical analysis was conducted using ratios of obtained biophysical data to pretreatment average of the contralateral normal breast tissue. Residual Cancer Burden (RCB) index was used to evaluate residual disease after treatment with NAC. RCB scores and classes were determined in 24 of the 27 surgical tissue specimens and these were compared to the NIRST data. RCB data for 3 patients were excluded: 2 patients had undergone positive excisional lymph node biopsy prior to NAC and 1 patient had surgery at an outside hospital. Results: Of the 27 patients, 7 had triple negative BC and 13 had HER-2 positive BC. The change in total hemoglobin (ΔHb-T %) after the first cycle of NAC when compared to the pre-treatment total hemoglobin was determined to be the best predicting factor for RCB (p-value <0.001). The Pearson correlation coefficient was calculated for both RBC class and RBC score (0.7 and 0.6). The significance of the correlation coefficient was evaluated using two-sided t-test and the resulting P-values of 0.006 and 0.001 respectively demonstrate that these correlations are statistically significant. Summary of the NIRST biophysical data and the correlating RCBPatientAgeERPRHer2RCB ScoreHbT -ΔHbT-pre136+-+0-139.933.30251---0-43.532.53341+++0-42.281.89430---0-43.061.59552---0-42.541.71663+++0-151.883.12760--+0-46.471.59852---0-42.721.96966--+0-110.022.471039--+0-9.091.101171+-+0-13.331.501252++-4.12153.201.581362++-3.7475.741.531470--+1.931100.521.631553++-3.4447.831.181641+++4.18929.841.511756+++4.44459.001.471850++-4.008-41.112.181954---3.05011.111.802063++-2.90020.001.502149---0.78026.321.902257++-1.8505.881.702347++-3.600-7.692.602470---3.10047.061.70 Conclusions: We have demonstrated a statistically significant correlation between ΔHb-T % after the first cycle of NAC and the RCB. These findings suggest the potential of using NIRST as an early assessment tool to evaluate response to NAC in BC patients and warrant further evaluation in a larger study. Citation Format: Batukbhai B, Jiang S, Bernhardt EB, Muller K, Cao X, Gui J, DiFlorio-Alexander RM, Chamberlin MD, Schwartz GN, Paulsen KD, Pogue BW, Kaufman PA. Near-infrared spectral tomography (NIRST): A prognostic assessment tool for predicting residual cancer burden (RCB) during neoadjuvant chemotherapy (NAC) in breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-02.

A 55-year-old African American man who was found down by a friend nine hours after being last seen at the same place was brought to the emergency department (ED) with encephalopathy, lactic acidosis, rhabdomyolysis, elevated troponin, acute kidney injury (AKI), and transaminitis. His urine drug screen (UDS) was positive for cocaine. Intravenous (IV) Narcan was given with minimal improvement in mental status. A computed tomography (CT) scan of the head and a CT scan of the cervical spine in the ED showed no acute findings. Due to hypoxia, the patient was eventually intubated. The patient also required a fasciotomy and eventually hyperbaric oxygen (HBO) therapy due to the left lower extremity wound. He was transferred to our facility for further care. Due to incomplete cognitive recovery, as the patient was oriented to self only, further neurological workup, including magnetic resonance imaging (MRI) of the brain, was obtained, which showed bilateral symmetric T2 FLAIR (Fluid attenuated inversion recovery) hyperintensity in the globus pallidus. The patient had slow and gradual deterioration with worsening encephalopathy, akinetic mutism, parkinsonian features, and seizures, which prompted further evaluation from neurology. The patient eventually underwent extensive workup, including a continuous video electroencephalogram (cvEEG), repeat MRI brain with and without contrast, lumbar puncture for cerebrospinal fluid (CSF) analysis, MRI brain with diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS). The patient was treated with multivitamin therapy and coenzyme Q10, but there was no significant benefit. We report a case of cocaine-induced leukoencephalopathy with findings like 'chasing the dragon encephalopathy' with a possible component of delayed post-hypoxic injury with underlying neuroinflammation.

MR elastography (MRE) has three essential elements: mechanical activation, MR motion estimation and shear modulus reconstruction. Mechanical activation of the brain is extremely difficult. Indeed it is much more difficult than actuation of other body parts because the skull and meninges form an excellent mechanical isolation system. Vibrations and impacts are heavily damped to protect the brain. Several methods have been used previously including whole head shaking using bite bar, a band around the head or actuators behind the head. We have found significant discomfort with all the methods we tried and that discomfort diminishes the utility dramatically because, when uncomfortable, patients do not complete examinations or introduce motion artifacts. All methods produce very small vibrations that are far below regulatory limits on vibration in the brain. We present evidence that the best way to couple shear waves to the brain is through the spinal cord. In a series of feline MRE examinations the largest shear motion occurred when the cerebellar motion was largest. The cerebellar motion was large where the spinal cord connects to the brain on every study that produced the most coherent, convergent solutions. Increased motion in the cerebellum occurred in 17 of 25 (68%) studies on seven animals. We postulate that one way to produce shear waves within the brain is through the spinal cord; i.e., that mechanical waves are transmitted along the cord and into the brain much more effectively than they are transmitted through the skull and meninges.