First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip

Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. Results: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. Conclusions: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes

Open-Ended Transmission Coaxial Probes for Sarcopenia Assessment

We developed a handheld, side-by-side transmission-based probe for interrogating tissue to diagnose sarcopenia-a condition largely characterized by muscle loss and replacement by fat. While commercial microwave reflection-based probes exist, they can only be used in a lab for a variety of applications. The penetration depth of these probes is only in the order of 0.3 mm, which does not even traverse the skin layer, and minor motion of the coaxial feedlines can completely dismantle the calibration. Our device builds primarily on the transmission-based concept that allows for substantially greater signal penetration depth operating over a very broad bandwidth. Additional features were integrated to further improve the penetration, optimize the geometry for a more focused planar excitation, and juxtapose the coaxial apertures for more controlled interrogation. The larger coaxial apertures further increased the penetration depth while retaining the broadband performance. Three-dimensional printing technology made it possible for the apertures to be compressed into ellipses for interrogation in a near-planar geometry. Finally, fixed side-by-side positioning provided repeatable and reliable performance. The probes were also not susceptible to multipath signal corruption due to the close proximity of the transmitting and receiving apertures. The new concept worked from 100 MHz to over 8 GHz and could sense property changes as deep as 2-3 cm. While the signal changes due to deeper feature aberrations were more subtle than for signals emanating from the skin and subcutaneous fat layers, the large property contrast between muscle and fat is a sarcopenic indication that helps to distinguish even the deepest objects. This device has the potential to provide needed specificity information about the relevant underlying tissue

Decrease in the Size of Fat-Enlarged Axillary Lymph Nodes and Serum Lipids after Bariatric Surgery

Background: Ectopic fat deposition in obesity is associated with organ dysfunction; however, little is known about fat deposition within the lymphatic system and associated lymphatic dysfunction. Methods: One hundred fifty-five women who underwent routine screening mammography before and after a Roux-en-y gastric bypass or a sleeve gastrectomy were retrospectively reviewed and after excluding women without visible nodes both before and after bariatric surgery, 84 patients were included in the final analysis. Axillary lymph node size, patient weight in kilograms, body mass index, and a diagnosis of hypertension, type 2 diabetes, and dyslipidemia were evaluated before and after surgery. Binary linear regression models and Fischer’s exact test were used to evaluate the relationship between the size of fat-infiltrated axillary lymph nodes, patient age, change in patient weight, and diagnosis of hypertension, type 2 diabetes, and dyslipidemia. Results: Fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery with a mean decrease of 4.23 mm (95% CI: 3.23 to 5.2, p < 0.001). The resolution of dyslipidemia was associated with a decrease in lymph node size independent of weight loss (p = 0.006). Conclusions: Mammographically visualized fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery. The decrease in lymph node size was significantly associated with the resolution of dyslipidemia, independent of weight loss, age, and type of surgery

Association between fat‐infiltrated axillary lymph nodes on screening mammography and cardiometabolic disease

Abstract Objective Ectopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index (BMI). Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms. Methods A cross‐sectional study was conducted on 834 women presenting for full‐field digital screening mammography. The status of fat‐infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non‐alcoholic fatty liver disease. Results Fat‐infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p‐value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve). Conclusion Fat‐infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat‐infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography

Image guided near-infrared spectroscopy of breast tissue in vivo using boundary element method

We demonstrate quantitative functional imaging using image-guided near-infrared spectroscopy (IG-NIRS) implemented with the boundary element method (BEM) for reconstructing 3-D optical property estimates in breast tissue in vivo. A multimodality MRI-NIR system was used to collect measurements of light reflectance from breast tissue. The BEM was used to model light propagation in 3-D based only on surface discretization in order to reconstruct quantitative values of total hemoglobin (HbT), oxygen saturation, water, and scatter. The technique was validated in experimental measurements from heterogeneous breast-shaped phantoms with known values and applied to a total of seven subjects comprising six healthy individuals and one participant with cancer imaged at two time points during neoadjuvant chemotherapy. Using experimental measurements from a heterogeneous breast phantom, BEM for IG-NIRS produced accurate values for HbT in the inclusion with a <3% error. Healthy breast tissues showed higher HbT and water in fibroglandular tissue than in adipose tissue. In a subject with cancer, the tumor showed higher HbT compared to the background. HbT in the tumor was reduced by 9 μM during treatment. We conclude that 3-D MRI-NIRS with BEM provides quantitative and functional characterization of breast tissue in vivo through measurement of hemoglobin content. The method provides potentially complementary information to DCE-MRI for tumor characterization

In vivo quantitative imaging of normal and cancerous breast tissue using broadband diffuse optical tomography

Purpose: A NIR tomography system that combines frequency domain (FD) and continuous wave (CW) measurements was used to image normal and malignant breast tissues