An infrared 3D scanning device as a novel limb volume measurement tool in breast cancer patients.

BACKGROUND: Lymphedema is a common complication of breast cancer treatment that affects one in five breast cancer survivors, yet there is no reliable method to detect lymphedema in the subclinical range. The objective of this study was to determine the feasibility and reliability of using an infrared 3D scanning device (ISD) as a peri-operative limb volume measurement tool. METHODS: Fifteen patients were analyzed based on inclusion criteria. Peri-operative measurements were obtained using tape measure and an ISD. Volumes were calculated using a standard algorithm for tape measure and a custom algorithm for ISD measurements. Linear regression models were used to assess ISD and tape measurement volume and circumference correlation. One-way ANOVA was used to compare change in percent difference at set time points post-operatively (2-3 weeks, 4-6 weeks, and 7-12 weeks) for both ISD and tape measure. t tests for unequal variances with the Bonferroni correction were performed among these groups. RESULTS: There is a positive linear correlation (R2 = 0.8518) between absolute volume measurements by the ISD and tape measure. Analyses over 2-10 weeks post-operatively showed that the ISD was able to detect volume changes in both the unaffected and the affected arm. Furthermore, the affected arm tended to have a greater increase in volume in the majority of patients, indicating these patients could be at risk for lymphedema. CONCLUSIONS: Technology utilizing infrared 3D scanners can reliably measure limb volume pre- and post-treatment similarly to tape measure in a small sample of patients. Further research using 3D scanning technology with a longer follow up is warranted.

Assessing Arm Volume in People During and After Treatment for Breast Cancer: Reliability and Convergent Validity of the LymphaTech System.

BACKGROUND: There are challenges related to the accurate and efficient measurement of lymphedema in people with breast cancer. The LymphaTech 3D Imaging System (LymphaTech, Atlanta, GA, USA) is a mobile, noninvasive platform that provides limb geometry measurements. OBJECTIVE: The objective of this study was to estimate the reliability and validity of the LymphaTech for measuring arm volume in the context of women seeking care in a specialty breast cancer rehabilitation clinic. DESIGN: This was a cross-sectional reliability and convergent validity study. METHODS: People who had stage I to IV breast cancer with lymphedema or were at risk for it were included. Arm volume was measured in 66 participants using the LymphaTech and perometer methods. Test-retest reliability for a single measure, limb volume difference, and agreement between methods was analyzed for 30 participants. A method-comparison analysis was also used to assess convergent validity between methods. RESULTS: Both LymphaTech and perometer methods displayed intraclass correlation coefficients (ICCs) of ≥0.99. The standard errors of measurement for the LymphaTech and length-matched perometer measurements were nearly identical. Similar intraclass correlation coefficients (0.97) and standard errors of measurement (38.0-40.7 mL) were obtained for the between-limb volume difference for both methods. The convergent validity analyses demonstrated no systematic difference between methods. LIMITATIONS: The sample size was not based on a formal sample size calculation. LymphaTech measurements included interrater variance, and perometer measurements contained intrarater variance. CONCLUSIONS: The LymphaTech had excellent test-retest reliability, and convergent validity was supported. This technology is efficient and portable and has a potential role in prospective surveillance and management of lymphedema in clinical, research, and home settings.

Monitoring Leg Lymphedema Over the Course of Therapy Using an Infrared System.

Background: There are many techniques of monitoring leg lymphedema during physical therapy. Taking volumetric measurements with a tape measure is among the most common clinically, and changes in volume are typically used to measure therapy efficacy. This study shows how the Kinect infrared (IR) sensor with custom algorithms can assess leg circumferences and volumes comparable with tape measurements taken by a trained therapist while exploring regional leg changes to determine uniformity of change. Methods and Results: Leg volumes were measured in 38 lymphedema patients using the tape measure circumference method and the Kinect IR system. Changes in circumferences in various leg regions over the course of therapy were analyzed in 23 patients. The leg circumferences (R2 = 0.9522) and volumes ( R2 = 0.9847) strongly correlated between the two methods. The Bland-Altman analysis indicated a circumference percent different bias of 1.6 (6.2%), requiring a minor correction factor between the two methods. Over the course of therapy, patients with a reduction in leg volume, defined as a change >6.5% have greater reduction most distal to the body. Conclusion: The Kinect IR system explored can be used clinically for leg volume measurements to monitor leg lymphedema patients over the course of their therapy. Implementing analysis of regional leg changes can better inform physical therapy to improve efficacy of treatment.

A novel mouse tail lymphedema model for observing lymphatic pump failure during lymphedema development.

It has been suggested that many forms of secondary lymphedema in humans are driven by a progressive loss of lymphatic pump function after an initial risk-inducing event. However, the link between pump failure and disease progression has remained elusive due to experimental challenges in the clinical setting and a lack of adequate animal models. Using a novel surgical model of lymphatic injury, we track the adaptation and functional decline of the lymphatic network in response to surgery. This model mimics the histological hallmarks of the typical mouse tail lymphedema model while leaving an intact collecting vessel for analysis of functional changes during disease progression. Lymphatic function in the intact collecting vessel negatively correlated with swelling, while a loss of pumping pressure generation remained even after resolution of swelling. By using this model to study the role of obesity in lymphedema development, we show that obesity exacerbates acquired lymphatic pump failure following lymphatic injury, suggesting one mechanism through which obesity may worsen lymphedema. This lymphatic injury model will allow for future studies investigating the molecular mechanisms leading to lymphedema development.

Volumetric Assessment of Pediatric Vascular Malformations Using a Rapid, Hand-Held Three-Dimensional Imaging System.

The effect of percutaneous, surgical, and medical therapies for vascular malformations (VMs) is often difficult to quantify volumetrically using cross-sectional imaging. Volumetric measurement is often estimated with serial, expensive MRI examinations which may require sedation or anesthesia. We aim to explore whether a portable 3D scanning device is capable of rapid, accurate volumetric analysis of pediatric VMs. Using an iPad-mounted infrared scanning device, 3D scans of patient faces, arms, and legs were acquired over an 8-month study period. Proprietary software was use to perform subsequent volumetric analysis. Of a total of 30 unilateral VMs involving either the face, arms, or legs, 26 (86.7%) VMs were correctly localized by discerning the larger volume of the affected side compared to the normal contralateral side. For patients with unilateral facial VMs (n = 10), volume discrepancy between normal and affected sides differed compared with normal controls (n = 19). This was true for both absolute (60 cc ± 55 vs 15 cc ± 8, p = 0.03) as well as relative (18.1% ± 13.2 vs 4.0% ± 2.1, p = 0.008) volume discrepancy. Following treatment, two patients experienced change in leg volume discrepancy ranging from - 17.3 to - 0.4%. Using a portable 3D scanning device, we were able to rapidly and noninvasively detect and quantify volume discrepancy resulting from VMs of the face, arms, and legs. Preliminary data suggests this technology can detect volume reduction of VMs in response to therapy.

Use of a Novel Portable Three-Dimensional Imaging System to Measure Limb Volume and Circumference in Patients with Filarial Lymphedema.

The World Health Organization's Global Program to Eliminate Lymphatic Filariasis (LF) has reduced LF transmission worldwide, but millions remain affected by filarial lymphedema. Tools for clinically monitoring lymphedema in developing nations are limited. We tested a novel, portable, infrared three-dimensional imaging system (3DIS) against water displacement (WD) and tape measurement of limb circumference (TMLC) among patients with filarial leg lymphedema in Galle, Sri Lanka. Outcomes were accuracy and reproducibility of imaging system measurements. In parallel, we also tested the reproducibility of skin thickness ultrasound (STU) measurements. We examined 52 patients (104 limbs) with lymphedema of stages 0-6 (N = 28, 19, 20, 21, 2, 4, and 10, respectively). 3DIS measurements correlated nearly perfectly with WD (r2 = 0.9945) and TMLC values (r2 > 0.9801). The median time required to acquire imaging system measurements for both legs was 2.1 minutes, compared with 17, 7, and 29 minutes, respectively, for WD, TMLC, and STU. Median interexaminer coefficients of variation (CVs) for volume measurements were 1.1% (interquartile range [IQR] 0.5-2.1%) for WD and 1.7% (IQR 1.2-2.4%) for the 3DIS. CVs for circumference measurements were 1.4% (IQR 0.8-2.4%) by TMLC and 1.3% (0.8-1.9%) by 3DIS. Median interexaminer CV for STU was 13.7% (IQR 8.5-21.3%). The portable imaging system noninvasively provided accurate and reproducible limb volume and circumference measurements in approximately 2 minutes per patient. This portable technology has the potential to greatly improve assessment and monitoring of lymphedema in the clinic and in the field.

Bridging the divide between pathogenesis and detection in lymphedema.

While our understanding of the lymphatic system has improved substantially in the past few decades, the translation of this knowledge into improved healthcare solutions for patients suffering from secondary lymphedema has been severely limited. The challenge facing clinicians is two-fold. First, there is no reliable, affordable, diagnostic capable of detecting the disease before symptoms of the lymphedema develop and the efficacy of treatment options becomes limited. Second, our understanding of the disease pathogenesis, its risk factors, and the underlying physiologic mechanisms is still in its infancy. These two challenges go hand in hand as limited diagnostic options have hindered our ability to understand lymphedema progression, and the lack of known underlying mechanisms involved in the disease prohibits the development of new diagnostic targets. This review serves to discuss the recent developments in clinical and lab research settings of both lymphedema diagnostic technologies and our understanding of the mechanisms driving disease risk and progression. We will show how these two lines of research are synergistically working with the ultimate goal of improving patient outcomes for those suffering from this horrible disease, identifying key areas of further research that are warranted to move the field forward and provide clinical relief for this neglected patient population.

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging.

The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (P(eff), pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased P(eff) of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of P(eff) and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease.

Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function.

Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.