Tissue Characterization Using an Electrical Bioimpedance Spectroscopy-Based Multi-Electrode Probe to Screen for Cervical Intraepithelial Neoplasia

The successful management of cervical intraepithelial neoplasia (CIN) with proper screening and treatment methods could prevent cervical cancer progression. We propose a bioimpedance spectroscopic measurement device and a multi-electrode probe as an independent screening tool for CIN. To evaluate the performance of this screening method, we enrolled 123 patients, including 69 patients with suspected CIN and 54 control patients without cervical dysplasia who underwent a hysterectomy for benign disease (non-CIN). Following conization, the electrical properties of the excised cervical tissue were characterized using an electrical bioimpedance spectroscopy-based multi-electrode probe. Twenty-eight multifrequency voltages were collected through the two concentric array electrodes via a sensitivity-optimized measurement protocol based on an electrical energy concentration method. The electrical properties of the CIN and non-CIN groups were compared with the results of the pathology reports. Reconstructed resistivity tended to decrease in the CIN and non-CIN groups as frequency increased. Reconstructed resistivity from 625 Hz to 50 kHz differed significantly between the CIN and non-CIN groups (p < 0.001). Using 100 kHz as the reference, the difference between the CIN and non-CIN groups was significant. Based on the difference in reconstructed resistivity between 100 kHz and the other frequencies, this method had a sensitivity of 94.3%, a specificity of 84%, and an accuracy of 90% in CIN screening. The feasibility of noninvasive CIN screening was confirmed through the difference in the frequency spectra evaluated in the excised tissue using the electrical bioimpedance spectroscopy-based multi-electrode screening probe.

A Randomized Clinical Trial of Bioimpedance Spectroscopy or Tape Measure Triggered Compression Intervention in Chronic Breast Cancer Lymphedema Prevention

Background: This study compared rates of progression to chronic breast cancer-related lymphedema (defined as a greater than or equal to 10% arm volume change from baseline requiring complex decongestive physiotherapy (CDP) ) following an intervention for subclinical lymphedema (S-BCRL) triggered by bioimpedance spectroscopy (BIS) or by tape measurement (TM). Methods and Results: This stratified, randomized, international trial enrolled new breast cancer patients undergoing: mastectomy/partial mastectomy, axillary treatment (dissection, sentinel lymph node biopsy >6 nodes or radiation), radiation therapy (chest wall/ breast, supraclavicular fossa), or taxane-based chemotherapy. Following post-surgery eligibility reassessment, centralized, 1:1 randomization to prospective surveillance by BIS or TM occurred. S-BCRL detection triggered a 4-week, 12-hour per day, compression sleeve and gauntlet intervention. The primary outcome (n=209), rates of post-intervention progression to CDP, were assessed over three years. Between June 24, 2014 and September 11, 2018, 1,200 patients were enrolled, 963 randomized (BIS n=482;TM n=481) and 879 analyzed (BIS n=442;TM n=437). Median follow-up was 32.9 months (IQR=22,35). BIS patients triggered an intervention at a lower rate than TM patients (20.1%, n=89 vs 27.5%, n=120, p = 0.011). Median months to trigger was longer with BIS than TM (9.7; 95%CI,8.2-12.6 vs 3.9; 95%CI,2.8-4.5, p = 0.001). Overall, 14.4%(n=30) progressed post-intervention, with reduced likelihood for BIS patients than TM patients (7.9%, n=7 vs 19.2%, n=23; RR=0.41; 95%CI,0.13-0.81; absolute reduction 11.3%; 95%CI,2.3%-20.3%; p = 0.016). Conclusions: As compared to TM, BIS provides a more precise identification of patients likely to benefit from an early compression intervention.

The equivalence of hydration status measured by the Fresenius BCM and the Cella Bioimpedance Spectroscopy devices on hemodialysis patients

BackgroundFluid management is a serious challenge for patients undergoing hemodialysis therapy (HD). Bioimpedance spectroscopy (BIS) is a promising technique to help with clinical hydration (HYD) assessment. The Fresenius Medical Care (FMC) Body Composition Monitor (BCM) is the standard but is large and expensive. Cella Medical has introduced a small wireless BIS device. This study compared the HYD status predicted by the two devices.MethodsFollowing the FMC BCM device manual guidelines, measurements of BIS were made wrist-ankle using typical ECG electrodes on the non-fistula side of HD patients pre dialysis while in their normal supine position. As usual, patients were measured before their normal time of therapy with the BCM. The Cella measurements were then performed within two minutes.ResultsForty-two HD patients (M=64%, age=64±30 yrs.), were measured. One patient data was removed. The mean BCM HYD status was 1.86 l, SD 1.46 l, and SEM 0.22 l. Cella was 1.806 l, SD 1.36 l, and the SEM 0.21 l. The 95% difference confidence interval (CI) was -0.66 to 0.55 l. The Pearson’s correlation (r) was r^2 = 0.85 (p<0.00001). There was no proportional bias: the offset was -0.056 l, and K=1.010. The limits of agreement (LOA) analysis showed a mean difference of 0.56 l, and limits d ±2SD = (−1.192 l, 1.081 l), indicating 95% of the difference will lie within these limits. To evaluate equivalence, we performed two one-sided t-tests (TOST). When the bounds were reduced to the limit =0.47 l and -0.59 l, we obtained a 0.046 p-value (alpha =0.05), at 80% statistical power. For 26% of the subjects, the difference was <0.1 l, for 43% <0.25 l, for 71% <0.5 l, for 83% <0.75 l, for 90% <1.0 l, and for 9.5% (4 patients) more than 1 l. Only two cases (4.8%) were just over the ±2SD limit.ConclusionThis study suggests the BCM and Cella devices can be used interchangeably.

COMPARISON OF PEROMETRY-BASED VOLUMETRIC ARM MEASUREMENTS AND BIOIMPEDANCE SPECTROSCOPY FOR EARLY IDENTIFICATION OF LYMPHEDEMA IN A PROSPECTIVELY-SCREENED COHORT OF BREAST CANCER PATIENTS

Breast cancer-related lymphedema (BCRL) affects more than one in five women treated for breast cancer, and women remain at lifelong risk. Screening for BCRL is recommended by several national and international organizations for women at risk of BCRL, and multiple methods of objective screening measurement exist. The goal of this study was to compare the use of perometry and bioimpedance spectroscopy (BIS) for early identification of BCRL in a cohort of 138 prospectively screened patients. At each screening visit, a patient's relative volume change (RVC) from perometer measurements and change in L-Dex from baseline (ΔL-Dex) using BIS was calculated. There was a negligible correlation between RVC and ΔL-Dex (r=0.195). Multiple thresholds of BCRL were examined: RVC ≥5% and ≥10% as well as and ΔL-Dex ≥6.5 and ≥10. While some patients developed an elevated RVC and ΔL-Dex, many demonstrated elevations in only one threshold category. Moreover, the majority of patients with RVC ≥5%, ΔL-Dex ≥6.5, or ΔL-Dex ≥10 regressed to non-elevated measurements without intervention. These findings suggest a role for combining multiple screening methods for early identification of BCRL; furthermore, BCRL diagnosis must incorporate patient symptoms and clinical evaluation with objective measurements obtained from techniques such as perometry and bioimpedance spectroscopy.