Research

Studies Related to Spectroscopy for Detecting Head & Neck Cancer

The ability to detect cancer cells in head and neck tissue is critical for diagnosis and treatment of head and neck cancer (HNC). Although tissue biopsy and histological analysis is the gold standard for detecting HNC cells, it is invasive, time-consuming, and expensive, requiring the work of several medical specialists.

Spectroscopy – the study of how light interacts with tissues – offers a relatively inexpensive, non-invasive alternative to cancer cell detection. The premise of this approach is that light exhibits different refraction patterns when it interacts with cancer cells instead of healthy cells due to differences in cellular micro-architecture, or in other words: light that has bounced off of cancer cells looks different from light that has bounced off of healthy cells.

Dr. Irving Bigio and the Biomedical Optics Lab at Boston University have pioneered the application of elastic scattering spectroscopy (ESS) for cancer cell detection using devices made up of a lamp, to generate light; a probe, to direct light onto and collect light from tissue; a spectrometer, to generate light spectral data; and a computer, to operate the device and record light spectra. ESS algorithms developed using artificial intelligence and machine learning techniques can distinguish light that has interacted with cancer cells from light that has interacted with healthy cells. Each ESS measurement takes less than a second to capture, record and analyze, requiring no special dyes, lighting, pathology expertise or highly technical equipment. The Biomedical Optics Lab and the OTO-COATI Lab have teamed up to develop ESS algorithms that could improve the diagnosis and treatment of head & neck cancer.

Validation of Elastic Scattering Spectroscopy for Intra-operative Margin Guidance during Oral Cancer Resection

Contributing Lab Faculty: Gregory Grillone, MD (PI) & Gintas Krisciunas, PhD, MPH, MA

Contributing Lab Staff & Students: Lucas Berry, Devin Lucas, & Gabriele Spokas

Collaborating Investigators: Irving Bigio, PhD – Boston University; John Gooey, MBBS – VA Boston Healthcare System; Miriam O’Leary, MD – Tufts Medical Center

Funding Source: NIDCR/NIH (1R01DE029862)

Oral (mouth) cancer is primarily treated by surgical resection. During resection, surgeons check to see if they’ve removed all the cancer by sending tissue samples at the edge (or margin) of the tumor to pathologists, who rapidly analyze the tissue samples and report the results back to the surgeon in a process called frozen sectioning. Since frozen sectioning consumes time and resources that ultimately increase the duration and cost of the surgery, the entire tumor margin cannot be assessed at frozen section, leaving surgeons to pick the most suspicious tissue sites to sample and send to pathologists based on appearance alone. ESS has the potential to help surgeons quickly and non-invasively identify all of the suspicious tissue sites within a margin based on spectral representations of the tissue’s micro-architecture, which could improve frozen sectioning efficiency and prevent cancer recurrence caused by stray cancer cells being left behind during surgery. The present study aims to develop ESS algorithms for detection of oral cancer during surgery by collecting ESS measures and tissue samples from patients being treated at several Boston-area hospitals.

Detecting Laryngeal Cancer by Applying Light Scattering Spectroscopy to the Oral Cavity – A Pilot Study

Contributing Lab Faculty: Gregory Grillone, MD (PI), Gintas Krisciunas PhD, MPH, MA, & Lauren Tracy, MD

Contributing Lab Staff & Students: Lucas Berry, Gabriele Spokas, & Mitali Sakharkar

Collaborating Investigators: Irving Bigio, PhD – Boston University

Leukoplakia (abnormal white spots) of the larynx (voice box) is a serious finding given that it can transform into laryngeal cancer. ENT specialists monitor patients with laryngeal leukoplakia by examining them with a laryngoscope (lighted tube), and taking samples of the leukoplakic tissue to send to pathologists, who test it for cancer. This monitoring process is both costly and burdensome for the patient, requiring frequent visits to the ENT over several years. ESS has the potential to lessen the burden of this process by providing a faster, less invasive method of assessing laryngeal cancer risk that could be performed by non-specialist providers. Based on the concept of field cancerization, which suggests that oral cavity (mouth) tissue of patients with benign laryngeal leukoplakia is substantially different from oral cavity tissue of patients with malignant laryngeal cancer, the present pilot study aims to assess the diagnostic potential of ESS for laryngeal leukoplakia by collecting ESS measures from patients with benign laryngeal leukoplakia and patients with malignant laryngeal cancer.

Characterization of Oral Cavity Sub-sites via Elastic Scattering Spectroscopy

Contributing Lab Faculty: Gregory Grillone, MD & Gintas Krisciunas PhD, MPH, MA

Contributing Lab Staff & Students: Gabriele Spokas, & Mitali Sakharkar (PI)

Collaborating Investigators: Irving Bigio, PhD – Boston University

Although ESS has the potential for several diagnostic applications based on measures of the oral cavity, its unknown whether this potential could vary by anatomic site. For example, an ESS measure of the tongue may be different from an ESS measure of the gum, and that difference might affect the accuracy of ESS algorithms. The present study aims to investigate this possibility by collecting ESS measures from several different anatomic sites within the oral cavities of healthy individuals. The ESS data generated from this study could be used to refine ESS diagnostic algorithms.

Studies Related to Acute Respiratory Failure

Acute respiratory failure (ARF) occurs when a patient’s medical condition leaves them unable to breathe or protect their airway on their own, requiring a mechanical ventilator to breathe for them via an endotracheal tube (ETT) or tracheostomy (port in the neck/throat). Intubation – the process of inserting an ETT into a patient’s airway – can cause damage to the airway and adjacent anatomical structures. Because of this, ARF survivors are susceptible to severe and potentially life-threatening complications after the tube is removed (post-extubation) like stridor, laryngeal edema, dysphagia, and aspiration, which can lead to adverse outcomes including pneumonia, re-intubation, prolonged hospital stay, and/or death.

The OTO-COATI lab is a part of a nation-wide consortium, led by Dr. Marc Moss at the University of Colorado, which studies complications related to ARF. This consortium elucidates pertinent findings by collecting data from ARF patients’ post-extubation swallow screen results, results of fiberoptic endoscopic examinations of swallow (FEES), and medical records generated during stays in intensive care units (ICUs). The goal driving the consortium’s past and future findings is to develop robust assessments and interventions that will lessen the frequency and burden of complications associated with ARF survivorship.

Aspiration in Acute Respiratory Failure Survivors

Contributing Lab Faculty: Gintas Krisciunas, PhD, MPH, MA (PI)

Contributing Lab Staff & Students: Grace Chow, Devin Lucas, & Gabriele Spokas

Collaborating Investigators: Nicholas Hill, MD – Tufts University; Joseph Levitt, MD MS – Stanford University; Marc Moss, MD – University of Colorado Denver; Jonathan Siner, MD – Yale University

Funding Source: NINR/NIH (1R01NR019989)

While post-extubation dysphagia and aspiration are common occurrences, their underlying mechanisms are poorly understood, making them difficult to predict. In one of our previous studies of ARF survivors, we made several characterizations of post-extubation dysphagia and aspiration that supported the development of a novel clinical predictive tool that relies on patients’ medical factors and swallow screen results to predict whether an ARF survivor will aspirate post-extubation. The present study aims to evaluate the accuracy of this novel tool, as well as that of several other commonly used swallow screens. ARF survivors are enrolled in the study shortly after extubation, given the swallow screens of interest, and given a FEES, which serves as a gold standard against which the swallow screen results can be compared for accuracy. Additional aims of this study include further characterization of post-extubation dysphagia and exploration of the relationship between ETT size and post-extubation outcomes.

Characterizing Post-extubation Laryngeal Edema in the Presence of Aspiration

Contributing Lab Faculty: Gintas Krisciunas, PhD, MPH, MA (PI)

Contributing Lab Staff & Students: Devin Lucas & Mitali Sakharkar

Collaborating Investigators: Marc Moss, MD – University of Colorado Denver

While both laryngeal edema and aspiration commonly occur in ARF survivors post-extubation, the correlation between the two events is unknown. The present study aims to investigate the correlation between the two events using data collected in a previous study.

Studies Related to Dysphagia Outcomes & Assessment

Dysphagia, or impairment of swallowing, can arise as many different presentations and severities, ranging from inconvenient to life-threatening. Dysphagia is primarily managed by speech language pathologists (SLPs). Instrumental exams, including the fiberoptic endoscopic exam of swallow (FEES) and video fluoroscopic swallow study (VFSS), are considered the gold standard diagnostic assessments of dysphagia.

There are few standardized guidelines for evaluating and treating dysphagia, making research on pertinent clinical outcomes and development of novel assessment tools necessary. The OTO-COATI Lab works with expert SLPs and dysphagia researchers from around the world to enhance and elucidate relevant diagnostic capabilities and clinical outcomes.

Validation of the Boston Residue And Clearance Scale (BRACS)

Contributing Lab Faculty: Gintas Krisciunas, PhD, MPH, MA (PI)

Contributing Lab Staff & Students: Lucas Berry, Arpita Edke, Winston Liu, & Mitali Sakharkar

Funding Source: BUMC CTSI

One of the cardinal signs of dysphagia is food or liquid left in the throat after a swallow (residue). While evaluating patients for dysphagia using FEES, SLPs often consider the severity of the residue problem (amount, location, clearance, sensation, etc.), but current residue rating scales focus on residue amount at discrete times and locations. BRACS is the only residue rating scale specifically built to measure the severity of the overall residue problem, but only preliminary testing has been reported. However, for this scale to be fully validated, we need to establish criterion validity by comparing our developed scale to other related scales and clinical outcomes and to test for external reliability. This study will use retrospectively collected clinical data to complete the validation of BRACS.

Reliability and Validity of Existing Scales to Measure the Residue Problem

Contributing Lab Faculty: Gintas Krisciunas, PhD, MPH, MA (PI)

Contributing Lab Staff & Students: Lucas Berry

Funding Source: BUMC CTSI

Addressing the same problem as the BRACS study (above), the present study aims to evaluate the reliability and validity of generic scales commonly used to assess the residue problem during FEES exams. This aim will be achieved using data collected from SLPs around the world as they assessed clips of FEES exams representing the broad spectrum of residue problem presentations.

Variation in Dysphagia Evaluation Practices

Contributing Lab Faculty: Gintas Krisciunas, PhD, MPH, MA (PI)

Contributing Lab Staff & Students: Lucas Berry & Arpita Edke

Funding Source: BUMC CTSI

Variation in care can occur in the absence of clear, empirically supported clinical guidelines that are known to promote optimal patient outcomes and appropriate use of health care resources. Given a lack of evidence-based algorithms for choosing the type or number of dysphagia associated assessments, the present study seeks to use retrospective medical record data to determine whether there was variation in administration of instrumental dysphagia assessments (e.g. FEES, VFSS) or patient reported outcome measures (PROMs) related to dysphagia in an outpatient clinic.

Studies Related to Biofeedback for Voice Disorders

When a person’s perilaryngeal muscles (muscles connected to the voice box) are over-active, they have vocal hyperfunction (VH). VH is associated with the most common types of voice disorders, including those that happen after repeated trauma to the vocal cord tissue (e.g. nodules and polyps) and vocal deterioration that occurs without a clear medical cause (muscle tension dysphonia).

The OTO-COATI lab studies VH in collaboration with the Vocal Hyperfunction Clinical Research Center (VHCRC) at Massachusetts General Hospital, which is led by Robert Hillman, PhD, CCC-SLP, research director and co-director of the Mass General Voice Center. The VHCRC is is an interdisciplinary, multi-institutional research program which integrates many types of data to attain a better understanding of the multiple causative factors and disordered physiological processes associated with VH in order to develop new, more effective methods for prevention, diagnosis and treatment.

Ambulatory monitoring of vocal function to improve voice disorder assessment

Contributing Lab Faculty: Lauren Tracy, MD (PI) & Gintas Krisciunas, PhD, MPH, MA

Contributing Lab Staff & Students: Grace Chow

Collaborating Investigators: Robert Hillman, PhD, CCC-SLP – MGH Institute of Health Professions; Cara Stepp, PhD – Boston University

Funding Source: NIDCD/NIH (5P50DC015446)

The ability to monitor vocal activity throughout a patient’s day has the potential to enhance clinical management of VH. One proposed way to achieve this ability is to place an accelerometer on the surface of a patient’s neck, where it can record the vibrations associated with vocal activity. The present study aims to assess and enhance the clinical utility of such accelerometers by asking patients with VH and healthy matched controls to wear them most of the day, for several days. In addition to the data generated by the accelerometers, data are collected from comprehensive voice assessments of and relevant surveys completed by subjects.

Preliminary studies to test the effect of ambulatory voice biofeedback in small groups of patients with vocal hyperfunction

Contributing Lab Faculty: Lauren Tracy, MD (PI) & Gintas Krisciunas, PhD, MPH, MA

Contributing Lab Staff & Students: Grace Chow

Collaborating Investigators: Robert Hillman, PhD, CCC-SLP – MGH Institute of Health Professions; Cara Stepp, PhD – Boston University; Jarrad Van Stan, PhD, CCC-SLP – Mass General Voice Center

Funding Source: NIDCD/NIH (5P50DC015446)

The traditional approach to treating patients for VH-associated disorders is attending weekly voice therapy sessions in which patients are trained to use their voice in ways that avoid inefficient or abusive patterns of vocal behavior. A limitation of this approach is that the training that takes place during the voice therapy sessions does not always carryover to patients’ daily use of their voices. A possible solution to this limitation is providing patients with ambulatory voice biofeedback whereby they’re shown how they’ve used their voices throughout the day (as measured by an accelerometer) on a smart device. The present study aims to determine whether such ambulatory biofeedback can improve voice training carryover compared to traditional voice therapy without biofeedback.