Review of intravascular lithotripsy for treating coronary, peripheral artery, and valve calcifications.

Management of intracoronary calcium (ICC) continues to be a challenge for interventional cardiologists. There have been significant advances in calcium treatment devices. However, there still exists a knowledge gap regarding which devices to choose for the treatment of ICC. The purpose of this manuscript is to review the principles of intravascular lithotripsy (IVL) and clinical data. The technique of IVL will then be compared to alternative calcium treatment devices. Clinical data will be reviewed concerning the treatment of coronary, peripheral artery and valvular calcifications. Controversies to be discussed include how to incorporate IVL into your practice, what is the best approach for treating calcium subtypes, how to approach under-expanded stents, what is the ideal technique for performing IVL, how safe is IVL, whether imaging adds value when performing IVL, and how IVL fits into a treatment program for peripheral arteries and calcified valves.

Er:YAG laser brain surgery with vascular specific coagulation.

BACKGROUND AND OBJECTIVE: Erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation can effectively resect water-bearing tissues. Application of Er:YAG resection in neurosurgery is complicated by unpredictable bleeding in surgical field. Recently, an integrated theranostic system combining a dual-wavelength laser surgery system using a thulium (Tm) fiber-laser for coagulation and Er:YAG for resection, combined with optical coherence tomography (OCT) guidance was demonstrated for the in vivo resection of tumor tissue. However, lateral thermal spread in the range of 100s of micrometers is common due to lack of vascular specificity using a Tm fiber-laser for coagulation. In this study, a vascular specific ytterbium (Yb) fiber-laser is utilized for enhanced photocoagulation during in vivo neurosurgery improving the precision of Er:YAG tissue resection with minimal lateral thermal spread. METHODS: Mice underwent stereotactic laser surgery with the proposed Yb/Er:YAG dual wavelength vascular specific neurosurgery in vivo. An OCT system (wavelength range 1310 ± 70 nm) and OCT derived angiography  images were used to record cortical images to confirm the coagulation of blood vessels and guide subsequent Er:YAG resection steps. After the laser surgery, mice were killed, and histological analysis was carried out using hematoxylin and eosin staining and Nissl staining to compare the lateral thermal spread with our previously reported Tm/Er:YAG neurosurgery where a continuous wave  Tm fiber-laser was used for coagulation. RESULTS: Coagulation scheme using a Yb fiber-laser allowed stoppage of blood flow in disparately sized blood vessels encountered in the mice brain. Histological analysis of murine brain slices post Yb/Er:YAG laser surgery yielded lower thermal spread compared with Tm/Er:YAG laser surgery, maximizing the efficiency in both hemostasis (blood flow stoppage) and maximizing tissue ablation efficiency with minimal residual thermal damage zone. CONCLUSION: In this study, a vascular specific coagulation scheme with Yb/Er:YAG dual-wavelength surgery is presented for neurosurgery. Additionally, Yb/Er:YAG study results are compared with that of a tissue coagulation approach in Tm/Er:YAG surgery previously reported to highlight improved coagulation, reduced nonspecific thermal damage and limited lateral thermal spread. Experimental results suggest that the developed dual-wavelength laser system can effectively resect neural tissues with high localization, minimal lateral thermal spread at the micrometer level while maintaining a bloodless surgical field.

Clinical Translation and Evaluation of a Handheld and Biocompatible Mass Spectrometry Probe for Surgical Use.

BACKGROUND: Intraoperative tissue analysis and identification are critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and evaluation of the MasSpec Pen technology for molecular analysis of in vivo and freshly excised tissues in the operating room (OR). METHODS: An Orbitrap mass spectrometer equipped with a MasSpec Pen interface was installed in an OR. A "dual-path" MasSpec Pen interface was designed and programmed for the clinical studies with 2 parallel systems that facilitated the operation of the MasSpec Pen. The MasSpec Pen devices were autoclaved before each surgical procedure and were used by surgeons and surgical staff during 100 surgeries over a 12-month period. RESULTS: Detection of mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries was achieved. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. CONCLUSIONS: This study shows that the MasSpec Pen system can be successfully incorporated into the OR, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be used to inform surgical and clinical decisions without disrupting tissue analysis workflows.

Differentiation of Brain Tumor Microvasculature From Normal Vessels Using Optical Coherence Angiography.

BACKGROUND AND OBJECTIVES: Despite rapid advances and discoveries in medical imaging, monitoring therapeutic efficacy for malignant gliomas and monitoring tumor vasculature remains problematic. The purpose of this study is to utilize optical coherence angiography for vasculature characterization inside and surrounding brain tumors in a murine xenograft brain tumor model. Features included in our analysis include fractional blood volume, vessel tortuosity, diameter, orientation, and directionality. STUDY DESIGN/MATERIALS AND METHODS: In this study, five tumorous mice models at 4 weeks of age were imaged. Human glioblastoma cells were injected into the brain and allowed to grow for 4 weeks and then imaged using optical coherence tomography. RESULTS: Results suggest that blood vessels outside the tumor contain a greater fractional blood volume as compared with vessels inside the tumor. Vessels inside the tumor are more tortuous as compared with those outside the tumor. Results indicate that vessels near the tumor margin are directed inward towards the tumor while normal vessels show a more random orientation. CONCLUSION: Quantification of vascular microenvironments in brain gliomas can provide functional vascular parameters to aid various diagnostic and therapeutic studies. © 2021 Wiley Periodicals LLC.

Integrating the MasSpec Pen to the da Vinci Surgical System for In Vivo Tissue Analysis during a Robotic Assisted Porcine Surgery.

Minimally invasive robotic-assisted surgeries have been increasingly used as a first-line of treatment for patients undergoing oncologic surgeries. In-situ tissue identification is critical to guide tissue resection and assist decision-making. Traditional intraoperative histopathologic analysis of frozen tissue sections can be time-consuming and present logistical challenges which interrupt surgical workflows. We report the development and implementation of a laparoscopic, drop-in version of the MasSpec Pen device integrated into the da Vinci Xi Surgical system for in vivo tissue analysis in a robotic-assisted porcine surgery. We evaluated the performance of the drop-in MasSpec Pen during surgery by introducing the device into the animal upper gastrointestinal system and performing in vivo analyses of the stomach and liver, including charred and bloody tissues after electrocauterization. The molecular profiles obtained included ions tentatively identified as metabolites and lipids typically observed with MasSpec Pen analysis, without causing observable tissue damage. Statistical classifiers built to distinguish porcine liver and stomach tissues using the in vivo data yielded an overall tissue identification accuracy of 98% (n = 53 analyses). The results provide evidence that the drop-in MasSpec Pen developed can be used to acquire mass spectra in vivo during a robotic-assisted surgery and might be used as an in vivo tissue assessment tool to help guide surgical resections and streamline surgical workflows.

Optical coherence tomography image-guided smart laser knife for surgery.

BACKGROUND AND OBJECTIVE: Surgical oncology can benefit from specialized tools that enhance imaging and enable precise cutting and removal of tissue without damage to adjacent structures. The combination of high-resolution, fast optical coherence tomography (OCT) co-aligned with a nanosecond pulsed thulium (Tm) laser offers advantages over conventional surgical laser systems. Tm lasers provide superior beam quality, high volumetric tissue removal rates with minimal residual thermal footprint in tissue, enabling a reduction in unwanted damage to delicate adjacent sub-surface structures such as nerves or micro-vessels. We investigated such a combined Tm/OCT system with co-aligned imaging and cutting beams-a configuration we call a "smart laser knife." METHODS: A blow-off model that considers absorption coefficients and beam delivery systems was utilized to predict Tm cut depth, tissue removal rate and spatial distribution of residual thermal injury. Experiments were performed to verify the volumetric removal rate predicted by the model as a function of average power. A bench-top, combined Tm/OCT system was constructed using a 15W 1940 nm nanosecond pulsed Tm fiber laser (500 µJ pulse energy, 100 ns pulse duration, 30 kHz repetition rate) for removing tissue and a swept source laser (1310 ± 70 nm, 100 kHz sweep rate) for OCT imaging. Tissue phantoms were used to demonstrate precise surgery with blood vessel avoidance. Depth imaging informed cutting/removal of targeted tissue structures by the Tm laser was performed. RESULTS: Laser cutting was accomplished around and above phantom blood vessels while avoiding damage to vessel walls. A tissue removal rate of 5.5 mm3 /sec was achieved experimentally, in comparison to the model prediction of approximately 6 mm3 /sec. CONCLUSION: We describe a system that combines OCT and laser tissue modification with a Tm laser. Simulation results of the tissue removal rate using a simple model, as a function of average power, are in good agreement with experimental results using tissue phantoms. Lasers Surg. Med. 50:202-212, 2018. © 2017 Wiley Periodicals, Inc.

In situ process monitoring in selective laser sintering using optical coherence tomography.

Selective laser sintering (SLS) is an efficient process in additive manufacturing that enables rapid part production from computer-based designs. However, SLS is limited by its notable lack of in-situ process monitoring when compared to other manufacturing processes. We report the incorporation of optical coherence tomography into an SLS system in detail and demonstrate access to surface and sub-surface features. Video frame rate cross-sectional imaging reveals areas of sintering uniformity and areas of excessive heat error with high temporal resolution. We propose a set of image processing techniques for SLS process monitoring with OCT and report the limitations and obstacles for further OCT integration with SLS systems.

Fourier optics analysis of phase-mask-based path-length-multiplexed optical coherence tomography.

Optical coherence tomography (OCT) is an imaging technique that constructs a depth-resolved image by measuring the optical path-length difference between broadband light backscattered from a sample and a reference surface. For many OCT sample arm optical configurations, sample illumination and backscattered light detection share a common path. When a phase mask is placed in the sample path, features in the detected signal are observed, which suggests that an analysis of a generic common path OCT imaging system is warranted. In this study, we present a Fourier optics analysis using a Fresnel diffraction approximation of an OCT system with a path-length-multiplexing element (PME) inserted in the sample arm optics. The analysis may be generalized for most phase-mask-based OCT systems. A radial-angle-diverse PME is analyzed in detail, and the point spread function, coherent transfer function, sensitivity of backscattering angular diversity detection, and signal formation in terms of sample spatial frequency are simulated and discussed. The analysis reveals important imaging features and application limitations of OCT imaging systems with a phase mask in the sample path optics.

Detection of plaque structure and composition using OCT combined with two-photon luminescence (TPL) imaging.

BACKGROUND AND OBJECTIVES: Atherosclerosis and plaque rupture leads to myocardial infarction and stroke. A novel hybrid optical coherence tomography (OCT) and two-photon luminescence (TPL) fiber-based imaging system was developed to characterize tissue constituents in the context of plaque morphology. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo coronary arteries (34 regions of interest) from three human hearts with atherosclerotic plaques were examined by OCT-TPL imaging. Histological sections (4 µm in thickness) were stained with Oil Red O for lipid, Von Kossa for calcium, and Verhoeff-Masson Tri-Elastic for collagen/elastin fibers and compared with imaging results. RESULTS: Biochemical components in plaques including lipid, oxidized-LDL, and calcium, as well as a non-tissue component (metal) are distinguished by multi-channel TPL images with statistical significance (P < 0.001). TPL imaging provides complementary optical contrast to OCT (two-photon absorption/emission vs scattering). Merged OCT-TPL images demonstrate the distribution of lipid deposits in registration with detailed plaque surface profile. CONCLUSIONS: Results suggest that multi-channel TPL imaging can effectively identify lipid sub-types and different plaque components. Furthermore, fiber-based hybrid OCT-TPL imaging simultaneously detects plaque structure and composition, improving the efficacy of vulnerable plaque detection and characterization.

Path-length-multiplexed scattering-angle-diverse optical coherence tomography for retinal imaging.

A low-resolution path-length-multiplexed scattering angle diverse optical coherence tomography (PM-SAD-OCT) is constructed to investigate the scattering properties of the retinal nerve fiber layer (RNFL). Low-resolution PM-SAD-OCT retinal images acquired from a healthy human subject show the variation of RNFL scattering properties at retinal locations around the optic nerve head. The results are consistent with known retinal ganglion cell neural anatomy and principles of light scattering. Application of PM-SAD-OCT may provide potentially valuable diagnostic information for clinical retinal imaging.

Deep subsurface cavities in skin utilizing mechanical optical clearing and femtosecond laser ablation.

BACKGROUND AND OBJECTIVES: High precision subsurface ablation can be produced in transparent materials using femtosecond laser pulses and multiphoton absorption. Light scattering limits application of the same technique to most biological tissues. Previously, subsurface ablation was demonstrated at superficial depths (50-250 µm) in highly scattering tissues including murine skin and human sclera. We report application of mechanical optical clearing to produce deeper subsurface femtosecond ablation in rodent skin. Ability to target deeper structures in skin using subsurface ablation may allow novel clinical applications for dermatological laser surgery. STUDY DESIGN/MATERIALS AND METHODS: Operation of a prototype tissue optical clearing device (TOCD) was verified with white light photography in ex vivo rodent skin. A focused femtosecond beam transmitted through the TOCD and was scanned across rodent skin to produce subsurface ablation at increasing focal depths. Histological sections with H&E staining of the laser irradiated rodent skin were examined for subsurface ablation features following laser irradiation. RESULTS: Subsurface cavities were observed as deep as 1.7 mm below the skin surface in histological tissue sections. Diameter of subsurface cavities varied from tens of microns to over 100 µm. Subsurface cavities produced by scanning the focused femtosecond beam were contiguous and formed a continuous cut. Mechanical disruption of the overlying tissues was not observed. CONCLUSIONS: Mechanical optical clearing can be applied directly to in situ rodent skin and produces an optical clearing effect. High precision subsurface ablation can be produced at positions substantially deeper than previously demonstrated. Future studies may be targeted in in vivo human skin to investigate potential clinical applications of subsurface femtosecond ablation using mechanical optical clearing.

Excretion and toxicity of gold-iron nanoparticles.

Though gold nanoparticles have been considered bio-inert, recent studies have questioned their safety. To reduce the potential for toxicity, we developed a nanoclustering of gold and iron oxide as a nanoparticle (nanorose) which biodegrades into subunits to facilitate rapid excretion. In this present study, we demonstrate acid and macrophage lysosomal degradation of nanorose via loss of the near-infrared optical shift, and clearance of the nanorose in vivo following i.v. administration in C57BL/6 mice by showing gold concentration is significantly reduced in 11 murine tissues in as little as 31 days (P < 0.01). Hematology and chemistry show no toxicity of nanorose injected mice up to 14 days after administration. We conclude that the clustering design of nanorose does enhance the excretion of these nanoparticles, and that this could be a viable strategy to limit the potential toxicity of gold nanoparticles for clinical applications. FROM THE CLINICAL EDITOR: The potential toxicity of nanomaterials is a critically important limiting factor in their more widespread clinical application. Gold nanoparticles have been classically considered bio-inert, but recent studies have questioned their safety. The authors of this study have developed a clustering gold and iron oxide nanoparticle (nanorose), which biodegrades into subunits to facilitate rapid excretion, resulting in reduced toxicity.

Erratum: Tissue harvest with a laser microbiopsy (Erratum).

[This corrects the article DOI: 10.1117/1.JBO.27.12.125001.].

Intravascular laser lithotripsy for calcium fracture in human coronary arteries.

BACKGROUND: Electrical intravascular lithotripsy (E-IVL) uses shock waves to fracture calcified plaque. AIMS: We aimed to demonstrate the ability of laser IVL (L-IVL) to fracture calcified plaques in ex vivo human coronary arteries and to identify and evaluate the mechanisms for increased vessel compliance. METHODS: Shock waves were generated by a Ho:YAG (Holmium: yttrium-aluminium-garnet) laser (2 J, 5 Hz) and recorded by a high-speed camera and pressure sensor. Tests were conducted on phantoms and 19 fresh human coronary arteries. Before and after L-IVL, arterial compliance and optical coherence tomography (OCT) pullbacks were recorded, followed by histology. Additionally, microcomputed tomography (micro-CT) and scanning electron microscopy (SEM) were performed. Finite element models (FEM) were utilised to examine the mechanism of L-IVL. RESULTS: Phantom cracks were obtained using 230 µm and 400 µm fibres with shock-wave pressures of 84±5.0 atm and 62±0.4 atm, respectively. Post-lithotripsy, calcium plaque modifications, including fractures and debonding, were identified by OCT in 78% of the ex vivo calcified arteries (n=19). Histological analysis revealed calcium microfractures (38.7±10.4 µm width) in 57% of the arteries which were not visible by OCT. Calcium microfractures were verified by micro-CT and SEM. The lumen area increased from 2.9±0.4 to 4.3±0.8 mm2 (p<0.01). Arterial compliance increased by 2.3±0.6 atm/ml (p<0.05). FEM simulations suggest that debonding and intimal tears are additional mechanisms for increased arterial compliance. CONCLUSIONS: L-IVL has the capability to increase calcified coronary artery compliance by multiple mechanisms.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose.

BACKGROUND AND OBJECTIVES: The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. STUDY DESIGN/MATERIALS AND METHODS: Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 × 8 × 2 mm(3) ) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 µm in thickness) were also imaged by TPL microscopy. RESULTS: Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 µm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. CONCLUSIONS: Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions.