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Open Access Publications from the University of California

Scholarly Works (13 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2017)

In the span of electromagnetic wave band from microwave to X-rays, Interactions of biological tissue and light at the terahertz (THz) wavelength band (λ ~ 30m - 3mm) are particularly unique for two reasons. First, the THz band retains a large dielectric constant for water from the microwave region while its shorter wavelength enables imaging applications with < 1mm resolution. Second, the effect of scattering from typical soft tissue structures (i.e. cells, collagen matrix, etc.) is less in the THz band compared to that in higher-frequency bands (IR band and up). Using this balance of properties, our study applies non-invasive THz sensing to study diseases and conditions that compromise our body’s ability to balance water in tissues.

This study focuses on developing a novel medical imaging technology using THz frequency waves to accurately assess and image the tissue water content of the cornea, which is a critical refractive and protective component of the eye. In ophthalmology, most corneal disorders such as Fuchs endothelial dystrophy (failure of stromal hydration regulation), Keratoconus (corneal ectasia), pseudophakic bullous keratopathy (unintentionally damaged endothelial layer), and corneal graft rejection result in corneal edema. Corneal edema is a contributing factor leading to corneal opacity, and if left untreated, can lead to chronic vision impairment. Accurate corneal tissue water content (CTWC) measurement, therefore can help with early diagnosis and intervention for corneal diseases and further our understanding of the formation and progression of corneal disorders.

This work details the development of a THz remote-sensing technique based on rigorous electromagnetic model of cornea-THz interaction, and an imaging system that can be practically implemented in the clinical setting. A novel ophthalmic THz imaging system is designed and implemented to perform completely non-contact, all normal-incidence imaging of the corneal surface. The imaging system uses a wavelength independent quasioptical design that achieves a <1.4 mm spatial resolution at 650 GHz. The corneal hydration sensing capability of this imager is demonstrated in in vivo corneas. For the first time, THz images of a living cornea showed the onset of acute corneal edema from endothelial damage. The THz imaging system is currently being used in the first phase of the clinical study to evaluate healthy and diseased corneas of patients with corneal graft and corneal dystrophies.

    Cover page: Terahertz imaging and sensing for ophthalmic evaluation of corneal diseases
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2013)

    THz region (1 mm - 0.1 mm, or 300 GHz and 3 THz) of the electromagnetic spectrum attracts applications in medical imaging, with its high dielectric constant of water, low non-ionizing photon energy (0.4-40 meV), and robustness against scattering from rough surface interface. This study investigates THz optical imaging system design and engineering, and explores implementation of THz imaging method for application in remote sensing of physiological tissue. Specifically, the focus of this manuscript is to explore two important topics in remote sensing design, with analysis of quasi-optical systems design and effect of rough surface scattering in THz wavelength.

    An overview of THz imaging field and application to medical imaging are presented. A survey of current methods THz imaging and remote sensing scheme is made to provide context for system design consideration. As an example, the direct-detection THz imaging system is characterized, and used in experiments for the following sections.

    In the second section, a detailed analysis of commonly used quasi-optical component (off-axis parabolic mirrors) is performed to investigate its focusing properties at THz wavelength. Additional attention is directed to polarization aberration effect in the propagation of coherent, linearly polarized THz beam through series of mirrors.

    The third section applies Kirchhoff random rough surface scattering theory at THz region, and provides analysis of signal strength and variance in the signal-to-noise ratio (SNR) in imaging.

    Lastly, a beam-scanning imaging system is constructed and demonstrated as an effort toward practical clinical application. The system employs a spinning polygon mirror and Michelson interferometer based design to allow source, detector, and target to remain fixed and perform imaging at a dramatically faster speed. The system achieves a focused THz beam diameter of 1.66mm and a large depth of field of >25 mm, and acquisition speed of minimum 100 pixels/s. Images of characterization targets and ex vivo tissue samples are presented.

      Cover page: Terahertz Imaging and Remote Sensing Design for Applications in Medical Imaging
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2022)
        Creative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2019)
        A method to register THz and visible images of cutaneous burn wounds and to calibrate THz image data is presented. Images of partial and full thickness burn wounds in 9 rats were collected over 435 mins. = 7.25 hours following burn induction. A two-step process was developed to reference the unknown structure of THz imaging contrast to the known structure and the features present in visible images of the injury. This process enabled the demarcation of a wound center for each THz image, independent of THz contrast. Threshold based segmentation enabled the automated identification of air (0% reflectivity), brass (100% reflectivity), and abdomen regions within the registered THz images. Pixel populations, defined by the segmentations, informed unsupervised image calibration and contrast warping for display. The registered images revealed that the largest variation in THz tissue reflectivity occurred superior to the contact region at ~0.13%/min. Conversely the contact region showed demonstrated an ~6.5-fold decrease at ~0.02%/min. Exploration of occlusion effects suggests that window contact may affect the measured edematous response.
          Cover page: Methods for registering and calibrating in vivo terahertz images of cutaneous burn wounds.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2017)
          Accurate and early prediction of tissue viability is the most significant determinant of tissue flap survival in reconstructive surgery. Perturbation in tissue water content (TWC) is a generic component of the tissue response to such surgeries, and, therefore, may be an important diagnostic target for assessing the extent of flap viability in vivo. We have previously shown that reflective terahertz (THz) imaging, a non-ionizing technique, can generate spatially resolved maps of TWC in superficial soft tissues, such as cornea and wounds, on the order of minutes. Herein, we report the first in vivo pilot study to investigate the utility of reflective THz TWC imaging for early assessment of skin flap viability. We obtained longitudinal visible and reflective THz imagery comparing 3 bipedicled flaps (i.e. survival model) and 3 fully excised flaps (i.e. failure model) in the dorsal skin of rats over a postoperative period of 7 days. While visual differences between both models manifested 48 hr after surgery, statistically significant (p < 0.05, independent t-test) local differences in TWC contrast were evident in THz flap image sets as early as 24 hr. Excised flaps, histologically confirmed as necrotic, demonstrated a significant, yet localized, reduction in TWC in the flap region compared to non-traumatized skin. In contrast, bipedicled flaps, histologically verified as viable, displayed mostly uniform, unperturbed TWC across the flap tissue. These results indicate the practical potential of THz TWC sensing to accurately predict flap failure 24 hours earlier than clinical examination.
            Cover page: Non-invasive terahertz imaging of tissue water content for flap viability assessment.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2017)

            Objective

            In vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema.

            Methods

            A partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T2-weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds.

            Results

            For both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 μm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis.

            Conclusion

            This paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging.

            Significance

            The ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2024)
              SIGNIFICANCE: Spatial frequency domain imaging (SFDI) applies patterned near-infrared illumination to quantify the optical properties of subsurface tissue. The periocular region is unique due to its complex ocular adnexal anatomy. Although SFDI has been successfully applied to relatively flat in vivo tissues, regions that have significant height variations and curvature may result in optical property inaccuracies. AIM: We characterize the geometric impact of the periocular region on SFDI imaging reliability. APPROACH: SFDI was employed to measure the reduced scattering coefficient ( μ s ) and absorption coefficient ( μ a ) of the periocular region in a cast facial tissue-simulating phantom by capturing images along regions of interest (ROIs): inferior temporal quadrant (ITQ), inferior nasal quadrant (INQ), superior temporal quadrant (STQ), central eyelid margin (CEM), rostral lateral nasal bridge (RLNB), and forehead (FH). The phantom was placed on a chin rest and imaged nine times from an en face or side profile position, and the flat back of the phantom was measured 15 times. RESULTS: The measured μ a and μ s of a cast facial phantom are accurate when comparing the ITQ, INQ, STQ, and FH to its flat posterior surface. Paired t tests of ITQ, INQ, STQ, and FH μ a and μ s concluded that there is not enough evidence to suggest that imaging orientation impacted the measurement accuracy. Regions of extreme topographical variation, i.e., CEM and RLNB, did exhibit differences in measured optical properties. CONCLUSIONS: We are the first to evaluate the geometric implications of wide-field imaging along the periocular region using a solid tissue-simulating facial phantom. Results suggest that the ITQ, INQ, STQ, and FH of a generalized face have minimal impact on the SFDI measurement accuracy. Areas with heightened topographic variation exhibit measurement variability. Device and facial positioning do not appear to bias measurements. These findings confirm the need to carefully select ROIs when measuring optical properties along the periocular region.
                Cover page: Multimodal optical imaging of the oculofacial region using a solid tissue-simulating facial phantom.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2017)
                Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.
                  Cover page: Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)–Targeted Photothermal Therapy
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2017)
                  Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.
                    Cover page: Polypeptide-Based Gold Nanoshells for Photothermal Therapy
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2018)
                    Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.
                      Cover page: THz Imaging System for <i>in vivo</i> Human Cornea
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