Publications by authors named "Nitesh Katta"

7 Publications

  • Page 1 of 1

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

Clin Chem 2021 Jul 15. Epub 2021 Jul 15.

Department of Chemistry, The University of Texas at Austin, Austin, TX.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/clinchem/hvab098DOI Listing
July 2021

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

Lasers Surg Med 2021 Jun 15. Epub 2021 Jun 15.

Department of Biomedical Engineering, The University of Texas Austin, Austin, Texas, 78712, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lsm.23446DOI Listing
June 2021

Group Refractive Index of Nanocrystalline Yttria-Stabilized Zirconia Transparent Cranial Implants.

Front Bioeng Biotechnol 2021 19;9:619686. Epub 2021 Mar 19.

Laboratory of Thomas Milner, Department of Biomedical Engineering, University of Texas, Austin, TX, United States.

Transparent "Window to the Brain" (WttB) cranial implants made from a biocompatible ceramic, nanocrystalline Yttria-Stabilized Zirconia (nc-YSZ), were recently reported. These reports demonstrated chronic brain imaging across the implants in mice using optical coherence tomography (OCT) and laser speckle imaging. However, optical properties of these transparent cranial implants are neither completely characterized nor completely understood. In this study, we measure optical properties of the implant using a swept source OCT system with a spectral range of 136 nm centered at 1,300 nm to characterize the group refractive index of the nc-YSZ window, over a narrow range of temperatures at which the implant may be used during imaging or therapy (20-43°C). Group refractive index was found to be 2.1-2.2 for OCT imaging over this temperature range. Chromatic dispersion for this spectral range was observed to vary over the sample, sometimes flipping signs between normal and anomalous dispersion. These properties of nc-YSZ should be considered when designing optical systems and procedures that propagate light through the window, and when interpreting OCT brain images acquired across the window.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.619686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044953PMC
March 2021

Laser nanobubbles induce immunogenic cell death in breast cancer.

Nanoscale 2021 Feb 4;13(6):3644-3653. Epub 2021 Feb 4.

Department of Biomedical Engineering, The University of Texas at Austin, TX, USA.

Recent advances in immunotherapy have highlighted a need for therapeutics that initiate immunogenic cell death in tumors to stimulate the body's immune response to cancer. This study examines whether laser-generated bubbles surrounding nanoparticles ("nanobubbles") induce an immunogenic response for cancer treatment. A single nanosecond laser pulse at 1064 nm generates micron-sized bubbles surrounding gold nanorods in the cytoplasm of breast cancer cells. Cell death occurred in cells treated with nanorods and irradiated, but not in cells with irradiation treatment alone. Cells treated with nanorods and irradiation had increased damage-associated molecular patterns (DAMPs), including increased expression of chaperone proteins human high mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and heat shock protein 70 (HSP70). This enhanced expression of DAMPs led to the activation of dendritic cells. Overall, this treatment approach is a rapid and highly specific method to eradicate tumor cells with simultaneous immunogenic cell death signaling, showing potential as a combination strategy for immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr06587kDOI Listing
February 2021

Laser brain cancer surgery in a xenograft model guided by optical coherence tomography.

Theranostics 2019 26;9(12):3555-3564. Epub 2019 May 26.

University of Texas at Austin.

Higher precision surgical devices are needed for tumor resections near critical brain structures. The goal of this study is to demonstrate feasibility of a system capable of precise and bloodless tumor ablation. An image-guided laser surgical system is presented for excision of brain tumors in a murine xenograft model. The system combines optical coherence tomography (OCT) guidance with surgical lasers for high-precision tumor ablation (Er:YAG) and microcirculation coagulation (Thulium (Tm) fiber laser). A fluorescent human glioblastoma cell line was injected into mice and allowed to grow four weeks. Craniotomies were performed and tumors were imaged with confocal fluorescence microscopy. The mice were subsequently OCT imaged prior, during and after laser coagulation and/or ablation. The prior OCT images were used to compute three-dimensional tumor margin and angiography images, which guided the coagulation and ablation steps. Histology of the treated regions was then compared to post-treatment OCT images. Tumor sizing based on OCT margin detection matched histology to within experimental error. Although fluorescence microscopy imaging showed the tumors were collocated with OCT imaging, margin assessment using confocal microscopy failed to see the extent of the tumor beyond ~ 250 µm in depth, as verified by OCT and histology. The two-laser approach to surgery utilizing Tm wavelength for coagulation and Er:YAG for ablation yielded bloodless resection of tumor regions with minimal residual damage as seen in histology. Precise and bloodless tumor resection under OCT image guidance is demonstrated in the murine xenograft brain cancer model. Tumor margins and vasculature are accurately made visible without need for exogenous contrast agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.31811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587169PMC
June 2020

Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system.

Sci Transl Med 2017 Sep;9(406)

Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA.

Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary. The mass spectra obtained presented rich molecular profiles characterized by a variety of potential cancer biomarkers identified as metabolites, lipids, and proteins. Statistical classifiers built from the histologically validated molecular database allowed cancer prediction with high sensitivity (96.4%), specificity (96.2%), and overall accuracy (96.3%), as well as prediction of benign and malignant thyroid tumors and different histologic subtypes of lung cancer. Notably, our classifier allowed accurate diagnosis of cancer in marginal tumor regions presenting mixed histologic composition. Last, we demonstrate that the MasSpec Pen is suited for in vivo cancer diagnosis during surgery performed in tumor-bearing mouse models, without causing any observable tissue harm or stress to the animal. Our results provide evidence that the MasSpec Pen could potentially be used as a clinical and intraoperative technology for ex vivo and in vivo cancer diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aan3968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830136PMC
September 2017

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

Lasers Surg Med 2018 03 7;50(3):202-212. Epub 2017 Aug 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.

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 mm /sec was achieved experimentally, in comparison to the model prediction of approximately 6 mm /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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lsm.22705DOI Listing
March 2018