Khay M. Tan

Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study

BACKGROUND Biopsy surveillance protocols for the assessment of Barretts esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. OBJECTIVE The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. DESIGN A pilot feasibility study. SETTING Massachusetts General Hospital. PATIENTS A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barretts esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. INTERVENTION Volumetric laser endomicroscopy. MAIN OUTCOME MEASUREMENTS Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. RESULTS There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. LIMITATIONS This is a single-center feasibility study with a limited number of patients. CONCLUSION Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01439633.).

Flexible transbronchial optical frequency domain imaging smart needle for biopsy guidance

Lung cancer is the leading cause of cancer related death. Macroscopic imaging techniques such as computed tomography are highly sensitivity at detecting small, ≤ 2cm, peripheral pulmonary lesions (PPLs) in the lung but lack the specificity necessary for diagnosis. Bronchoscopy is a procedure routinely performed to diagnose PPLs but is hindered with a low diagnostic yield due to challenging lesion localization. We have developed a flexible transbronchial optical frequency domain imaging (TB-OFDI) catheter that functions as a ‘smart needle’ to confirm the needle placement within the target lesion prior to biopsy. The TB-OFDI smart needle consists of a flexible and removable OFDI catheter that operates within a 21-gauge transbronchial needle aspiration (TBNA) needle. The OFDI catheter can be easily removed from the needle to facilitate subsequent aspiration or biopsy acquisition. The OFDI imaging core consists of an angled-polished ball lens with a spot size of 25 μm at a working distance of 160 μm from the catheter sheath. The ball-lens was designed to have an ellipsoid shape in order to compensate for the astigmatism caused by encasing the optics within a protective sheath. Transbronchial imaging of inflated excised swine lung parenchyma with the TB-OFDI smart needle yielded clear images of alveoli. In-vivo transbronchial imaging was also performed on three swine with artificial lesions injected transthoracially. Our results suggest that the TB-OFDI smart needle may be a useful tool for guiding biopsy acquisition to increase the diagnostic yield of PPLs.

Assessment of smoke inhalation injury using volumetric optical frequency domain imaging in sheep models

Smoke inhalation injury is a serious threat to victims of fires and explosions, however accurate diagnosis of patients remains problematic. Current evaluation techniques are highly subjective, often involving the integration of clinical findings with bronchoscopic assessment. It is apparent that new quantitative methods for evaluating the airways of patients at risk of inhalation injury are needed. Optical frequency domain imaging (OFDI) is a high resolution optical imaging modality that enables volumetric microscopy of the trachea and upper airways in vivo. We anticipate that OFDI may be a useful tool in accurately assessing the airways of patients at risk of smoke inhalation injury by detecting injury prior to the onset of symptoms, and therefore guiding patient management. To demonstrate the potential of OFDI for evaluating smoke inhalation injury, we conducted a preclinical study in which we imaged the trachea/upper airways of 4 sheep prior to, and up to 60 minutes post exposure to cooled cotton smoke. OFDI enabled the visualization of increased mucus accumulation, mucosal thickening, epithelial disruption and sloughing, and increased submucosal signal intensity attributed to polymorphonuclear infiltrates. These results were consistent with histopathology findings. Bronchoscopic inspection of the upper airways appeared relatively normal with only mild accumulation of mucus visible within the airway lumen. The ability of OFDI to not only accurately detect smoke inhalation injury, but to quantitatively assess and monitor the progression or healing of the injury over time may provide new insights into the management of patients such as guiding clinical decisions regarding the need for intubation and ventilator support.

Optical coherence tomography (OCT) imaging of dynamic airway behavior in an asthma model (Conference Presentation)

To better understand bronchoconstriction in asthma, it is critical to dynamically visualize airway behavior in vivo. However, currently available imaging techniques do not have sufficient temporal and spatial resolution to investigate airway dynamics. We propose to use endobronchial Optical Coherence Tomography (OCT) to provide real-time cross-sectional images of airway dynamics with a high spatial resolution. Our aim was to study the structure and function of spatially distinct airways during tidal breathing (TB), breath-holds (BH) at end inspiration, and in a response to single deep inspiration (DI) and multiple DI (MDI) in a preclinical sheep asthma model. Anesthetized and mechanically ventilated sheep (n=3) were imaged with OCT in 4 dependent and 4 non-dependent airways at baseline and in methacholine constricted airways. We assessed airway morphology during TB, BH, DI and MDI maneuvers. The change in airway lumen area was found to be greater in the dependent airways compared to the non-dependent airways during TB (dependent: +14.9%, non-dependent: +6%) at baseline. Similarly, the dependent airways dilated more than the non-dependent airways in response to BH (dependent: +7.9%, non-dependent: +5.7%) in relaxed condition. Conversely, in the constricted lung, the DI and MDI maneuvers dilated the non-dependent airways (+13.6% DI, +44% MDI) more than the dependent airways (+6% DI, +15.5% MDI). Overall, dependent airways were more distensible than non-dependent airways during TB and BH, while this behavior was reversed following DI and MDI maneuvers in constricted airways possibly due to a greater local methacholine delivery due to gravitational dependencies on perfusion.

Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics (Conference Presentation)

Asthma is a chronic disease resulting in periodic attacks of coughing and wheezing due to temporarily constricted and clogged airways. The pathophysiology of asthma and the process of airway narrowing are not completely understood. Appropriate in vivo imaging modality with sufficient spatial and temporal resolution to dynamically assess the behavior of airways is missing. Optical coherence tomography (OCT) enables real-time evaluation of the airways during dynamic and static breathing maneuvers. Our aim was to visualize the structure and function of airways in healthy and Methacholine (MCh) challenged lung. Sheep (n=3) were anesthetized, mechanically ventilated and imaged with OCT in 4 dependent and 4 independent airways both pre- and post-MCh administration. The OCT system employed a 2.4 Fr (0.8 mm diameter) catheter and acquired circumferential cross-sectional images in excess of 100 frames per second during dynamic tidal breathing, 20 second static breath-holds at end-inspiration and expiration pressure, and in a response to a single deep inhalation. Markedly different airway behavior was found in dependent versus non-dependent airway segments before and after MCh injection. OCT is a non-ionizing light-based imaging modality, which may provide valuable insight into the complex dynamic behavior of airway structure and function in the normal and asthmatic lung.