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R Rox Anderson

Publications and source records attributed to R Rox Anderson.

At least 37 records · Page 2Linked to original sources

In vivo and ex vivo virtual biopsy of the liver with near-infrared, reflectance confocal microscopy.

The assessment of liver architecture is an essential part of the understanding of its physiology and pathology. Current fluorescence confocal microscopy methods face numerous drawbacks, such as cytotoxicity, quenching effect, potential negative ino- and chrono-tropic effects and leaking of fluorescent agents through the sinusoid fenestrations. The recently developed, near-infrared reflectance confocal microscopy allows high-resolution optical sectioning through intact tissues, without employing fluorescent stains, while contrast between structures is provided by the natural refractivity of the tissue. The aim of this study is to assess the utility of near-infrared reflectance confocal microscopy in the evaluation of the hepatic microscopic architecture in vivo and ex vivo. Rat livers were noninvasively examined in vivo and ex vivo with near-infrared reflectance confocal microscopy. Two experimental contrast agents were subsequently used to enhance particular structures. Parenchymal and vascular structures are readily identified, as well as some intracellular details. Differences between in vivo and ex vivo states were also observed. The use of contrast agents also highlights certain morphologic structures. In conclusion, near-infrared reflectance confocal microscopy stands as a useful adjunct technique to the study of hepatic parenchyma offering details equivalent to, if not surpassing traditional light microscopy.

Animals↗

Evaluation of human knee meniscus biopsies with near-infrared, reflectance confocal microscopy. A pilot study.

Knee cartilage biopsy is used to confirm the pathology in both clinical and experimental conditions and often guides diagnosis and therapeutic strategies. Current histopathological techniques are time consuming, induce tissue artefacts and often prevent further evaluation, once the tissue has been fixed. Hence, there is a potential need for a fast and nondestructive imaging technique for unfixed tissue. Near-infrared, reflectance confocal microscopy (CM) allows real-time, virtual sectioning of unstained, bulk tissue samples. This pilot study evaluates the use of CM in the assessment of meniscus histopathology in a series of 26 freshly-excised human meniscus samples compared to standard light microscopy of stained sections. CM images of the meniscus show cell and matrix detail, depicting morphologic features of collagen and elastic fibres, vessels and nerve endings. In addition, crystal deposits of gout and pseudogout are also demonstrable. Thus, CM is a novel imaging technique that could enable the pathologist to make a rapid microscopic evaluation of cartilage in a fresh and unfixed fashion.

Adult↗

Imaging the mucosa of the human vocal fold with optical coherence tomography.

OBJECTIVES: Discerning the layered microstructure of the vocal folds is critical for effective phonomicrosurgery. Optical coherence tomography (OCT), a noncontact, noninvasive technology that provides cross-sectional images by means of backscattered light, offers the potential for delineating these layers in vivo. METHODS: The glottal mucosa of 3 human cadaver larynges was imaged with conventional OCT and polarization-sensitive OCT (PS-OCT). Images were obtained through the epithelium and lamina propria. RESULTS: Although the superficial layer of the lamina propria appeared quite homogeneous, the outer surface of the superficial lamina propria was correlated with an increase in backscatter with OCT. The superficial lamina propria and vocal ligament were correlated with a marked increase in tissue birefringence with PS-OCT. CONCLUSIONS: This preliminary study demonstrates the capacity of OCT and PS-OCT for visualizing the layered microstructure of the vocal fold mucosa. We believe that these imaging techniques will have applications in the exploration of solutions to vocal fold scarring and in imaging vocal fold disorders in the clinic and operating room.

Cadaver↗

Transdermal microconduits by microscission for drug delivery and sample acquisition.

BACKGROUND: Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 microm diameter areas of human skin in vivo. METHODS: Microscissioning is achieved by a limited flux of accelerated gas: 25 microm inert particles passing through the aperture in a mask held against the stratum corneum. The particles scize (cut) tissue, which is removed by the gas flow with the sensation of a gentle stream of air against the skin. The resulting microconduit is fully open and may be between 50 and 200 microm deep. RESULTS: In vivo adult human tests show that microconduits reduce the electrical impedance between two ECG electrodes from approximately 4,000 Omega to 500 Omega. Drug delivery has been demonstrated in vivo by applying lidocaine to a microconduit from a cotton swab. Sharp point probing demonstrated full anaesthesia around the site within three minutes. Topical application without the microconduit required approximately 1.5 hours. Approximately 180 microm deep microconduits in vivo yielded blood sample volumes of several microl, with a faint pricking sensation as blood enters tissue. Blood glucose measurements were taken with two commercial monitoring systems. Microconduits are invisible to the unaided eye, developing a slight erythematous macule that disappears over days. CONCLUSION: Microscissioned microconduits may provide a minimally invasive basis for delivery of any size molecule, and for extraction of interstitial fluid and blood samples. Such microconduits reduce through-skin electrical impedance, have controllable diameter and depth, are fully open and, after healing, no foreign bodies were visible using through-skin confocal microscopy. In subjects to date, microscissioning is painless and rapid.

Administration, Cutaneous↗

Confocal reflectance imaging of head and neck surgical specimens. A comparison with histologic analysis.

BACKGROUND: Confocal reflectance microscopy (CRM) is an optical method of imaging tissue noninvasively without the need for fixation, sectioning, and staining as in standard histopathologic analysis. Image contrast is determined by natural differences in refractive indices of organelles and other subcellular structures within the tissues. Gray-scale images are displayed in real time on a video monitor and represent horizontal (en face) optical sections through the tissue. We hypothesized that CRM is capable of discerning histologic characteristics of different tissues in the head and neck. OBJECTIVES: To examine the microscopic anatomy of freshly excised head and neck surgical specimens en bloc using CRM and to compare the findings with those generated by conventional histologic analysis. DESIGN: This was a pilot observational cohort study. Bone, muscle, nerve, thyroid, parotid, and ethmoid mucosa from human surgical specimens were imaged immediately after excision. Confocal images were compared with corresponding routine paraffin-embedded, hematoxylin-eosin-stained sections obtained from the same tissue. RESULTS: Characteristic histologic features of various tissues and cell types were readily discernible by CRM and correlated well with permanent sections. However, in all tissues examined, there was less microscopic detail visible in the CRM images than was appreciated in paraffin-embedded histologic sections. CONCLUSIONS: The CRM images revealed cytologic features without the artifacts of histologic processing and thus may have the potential for use as an adjunct to frozen-section analysis in intraoperative consultation.

Cohort Studies↗

Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury.

BACKGROUND AND OBJECTIVES: We introduce and clinically examine a new concept of skin treatment called fractional photothermolysis (FP), achieved by applying an array of microscopic treatment zones (MTZ) of thermal injury to the skin. STUDY DESIGN/MATERIALS AND METHODS: Two prototype devices emitting at 1.5 microm wavelength provided a pattern of micro-exposures with variable MTZ density. Effects of different MTZ densities were tested on the forearms of 15 subjects. Clinical effects and histology were assessed up to 3 months after exposure. Treatment of photoaged skin on the periorbital area in an additional 30 subjects receiving four treatments over a period of 2-3 weeks was also tested. Tissue shrinkage and clinical effects were assessed up to 3 months after treatment. RESULTS: Pattern densities with spacing of 250 microm or more were well tolerated. Typical MTZ had a diameter of 100 microm and penetrated 300 microm into the skin. Reepithelialization was complete within 1 day. Clinical effects were assessed over a 3-month period. Histology at 3 months revealed enhanced undulating rete ridges and increased mucin deposition within the superficial dermis. Periorbital treatments were well tolerated with minimal erythema and edema. Linear shrinkage of 2.1% was measured 3 months after the last treatment. The wrinkle score improved 18% (P < 0.001) 3 months after the last treatment. CONCLUSIONS: FP is a new concept for skin restoration treatment. Safety and efficacy were demonstrated with a prototype device. Further clinical studies are necessary to refine the optimum parameters and to explore further dermatological applications.

Adult↗

Mechanisms of microvascular response to laser pulses.

"Selective photothermolysis" is widely used for treating vascular lesions. In order to understand mechanisms of response, we investigated fast events during pulsed laser treatment of microvessels. A high-speed (2000 fps) CCD camera and microscope were used to image hamster cheek pouch microvessels during and after 532 nm and 1064 nm laser pulse exposures. Pulse duration and fluence were varied systematically (1-50 ms, 0-600 J per cm2). Threshold fluences for fast events were determined. On a millisecond time-scale, a specific series of fast events occur, which are wavelength, fluence, irradiance, and pulse duration dependent. In order of increasing fluence we observed: blood coagulation, vasoconstriction, thread-like appearance of the treated vascular segment, vessel disappearance, intravascular cavitation, bubble formation, vessel wall rupture and hemorrhage, and shrinkage of perivascular tissue. With increasing pulse duration, the threshold fluences for coagulation, vessel disappearance, and cavitation increase, and cavitation becomes less violent, conforming to the vessel lumen. Intravascular cavitation did not always rupture the vessel wall, and is not the mechanism for immediate vessel disappearance, a desired endpoint for treating vascular lesions. The apparent mechanism for immediate vessel disappearance is contraction of intravascular blood and perivascular collagen after thermal denaturation. This study suggests that detecting fast events in humans, in real time, may provide useful feedback signals for "smarter" laser devices.

Animals↗

Office-based treatment of glottal dysplasia and papillomatosis with the 585-nm pulsed dye laser and local anesthesia.

Treatment of glottal papillomatosis and dysplasia was mirror-guided and performed in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. Presently, the primary treatment goals, which are disease regression and voice restoration or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. In fact, general anesthesia has been appropriately considered to be an acceptable source of morbidity for the promise of a precise procedure, which usually ensures airway safety and an optimal vocal outcome. However, patients with recurrent glottal papillomatosis and keratosis with dysplasia are typically monitored with various degrees of watchful waiting until there is a subjective judgment (on the part of the patient and surgeon) that the disease is more of a liability than is the procedure to treat it. Innovations in the 585-nm pulsed dye laser delivery system have allowed for its use in the clinic with local anesthesia through the working channel of a flexible fiberoptic laryngoscope. A prospective assessment was done on 51 patients in 82 cases of recurrent glottal papillomatosis (30) and dysplasia (52). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Five procedures could not be completed because of impaired exposure (2) or discomfort (3). Of those patients who could be treated, there was at least a 50% disease involution in 68 of 77 cases (88%) and 25% to 50% disease regression in the remaining 9 (12%). Patient self-assessment of the voice revealed that 34 of 77 were improved, 39 were unchanged, 4 were slightly worse, and none were substantially worse. These data confirm that diseased mucosa can be normalized without resection or substantial loss of vocal function. The putative mechanisms, which vary according to the fluence (energy) delivered by the laser, are photoangiolysis of sublesional microcirculation. denaturing of epithelial basement membrane linking proteins, and cellular destruction. Furthermore, this relatively safe, effective technique allowed for treatment of many patients (in a clinic setting) in whom classic surgery-related morbidity would have often delayed intervention.

Adult↗

Fire and ice.

Explore the source record for details and available documents.

Blood Coagulation↗

Selective cell targeting with light-absorbing microparticles and nanoparticles.

We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling. The extent of light-induced damage was investigated by cell lethality, by cell membrane permeability, and by protein inactivation. Strong particle size dependence was found for these interactions. A technique based on light to target endogenous particles is already being exploited to treat pigmented cells in dermatology and ophthalmology. With exogenous particles, phamacokinetics and biodistribution studies are needed before the method can be evaluated against photodynamic therapy for cancer treatment. However, particles are unique, unlike photosensitizers, in that they can remain stable and inert in cells for extended periods. Thus they may be particularly useful for prelabeling cells in engineered tissue before implantation. Subsequent irradiation with laser pulses will allow control of the implanted cells (inactivation or modulation) in a noninvasive manner.

Apoptosis↗

Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging.

More than a million cases of nonmelanoma skin cancers are diagnosed every year. Treatment of cancer patients could benefit greatly if a real-time, noninvasive, reliable, and cost-effective technique for delineating tumor margins were available. A novel multispectral dye-enhanced polarized light imaging technique that enables rapid imaging of large tumor fields is described. A tunable monochromatic light source and a CCD camera were employed as the imaging device. Linear polarizers were introduced into both the incident and collected light pathways in order to limit the measurement volume to the superficial tissue layers. To enhance the tumor contrast in the image, aqueous solutions of toluidine blue or methylene blue were topically applied to fresh thick skin excisions for several minutes. Then the specimens were rinsed in saline solution. Images were acquired before and after staining at the selected wavelengths. The two sets of wavelengths corresponding to the hemoglobin Soret absorption band and to the absorption bands of the dyes were used to demarcate the areas of enhanced hemoglobin and dye absorption, respectively. The resulting images demonstrate that staining significantly enhances contrast of the tumor in the image and enables reliable delineation of cancer. Locations and shapes of tumor lobules revealed by polarized light images closely correspond to those found in Mohs frozen sections for 41 specimens out of 45. The study demonstrates that the suggested technique has significant potential as a guidance tool in tumor excision surgery.

Basal Cell Carcinoma↗

Photodynamic therapy for cutaneous proliferative vascular tumors in a mouse model.

Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm2 of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (p< or =0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted.

Animals↗

585-nm pulsed dye laser treatment of glottal dysplasia.

Management of glottal dysplasia can be difficult and often results in a suboptimal treatment outcome. The surgeon and patient must cooperatively balance decisions regarding the effects of possible malignancy, vocal dysfunction, and recurrences leading to multiple use of general anesthetics. A pilot study was done in 57 cases (36 patients and 97 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 450-micros pulse width, 19 to 76-J/cm2 fluence, 1- to 2-mm spot size) in the treatment of vocal fold keratosis. Forty of the 57 cases had bilateral treatment. Phonomicrosurgical resection was done in 35 of the 57 cases after PDL treatment. Of this group, 10 cases were found to have hyperplasia, 21 dysplasia, 4 carcinoma in situ, and 1 carcinoma. One patient had phonomicrosurgical resection before PDL treatment. In 21 of the 57 cases, the disease was irradiated without resection (4 unilateral lesions and 17 bilateral lesions). Approximately 80% of the patients in this series had a greater than 70% reduction in the size of the lesion with the use of the PDL irrespective of whether they underwent resection. Clinical observation revealed no new anterior commissure web formation despite bilateral anterior commissure treatment in 28 of the 57 cases. The PDL enhanced the epithelial excision by improving hemostasis and by creating an optimal dissection plane between the basement membrane and the underlying superficial lamina propria. In this initial trial, the PDL provided relatively safe and effective treatment for glottal dysplasia. Analysis of patterns of recurrence will require longer follow-up.

Adult↗

Magnetite tattoos.

BACKGROUND AND OBJECTIVES: Tattoo removal is a significant problem. The extraction of magnetite (Fe(3)O(4)) ink tattoos by a magnetic field was investigated, with and without Q-switched laser treatment. STUDY DESIGN/MATERIALS AND METHODS: Magnetite particles (1.4 microm) were used to make mature, black skin tattoos on hairless albino rats. A Q-switched ruby laser (QSRL) 3.5 J/cm(2), 6.5-mm spot size, 40-nanosecond pulse width was used for treatment. Permanent magnets (1.4 T, 6-mm diameter) were tested to extract the magnetite particles, alone and after QSRL. Lightening of treated tattoos was measured from digital photographs, and the amount and distribution of magnetite in skin biopsies was scored blindly. RESULTS: External application of magnets on mature magnetite tattoos without prior QSRL treatment, did not significantly extract, lighten, darken, or change their histologic appearance. A magnetic field applied immediately after QSRL treatment extracted some ink when epidermal injury was present, and caused significant redistribution of magnetite into the upper dermis with vertical banding along magnetic field lines. When applied for 3 weeks following QSRL, magnets caused darkening of tattoos. CONCLUSIONS: Magnetite skin tattoos can be manipulated by external magnets, especially after Q-switched laser treatment. Magnetically-extractable tattoos may be feasible.

Albinism↗

Efficacy of erbium:yttrium-aluminum-garnet laser-assisted delivery of topical anesthetic.

BACKGROUND: Penetration through the stratum corneum limits effectiveness of topical anesthetics. OBJECTIVE: Our aim was to evaluate the effectiveness of 5% lidocaine (ELA-Max) cream applied after erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation of the stratum corneum. METHODS: Randomized, controlled, split-face comparison of anesthesia was performed on 12 volunteers. The stratum corneum was painlessly ablated with a low-fluence Er:YAG laser on half of the face, then the whole face was covered with ELA-Max cream for 60 minutes. Full-face laser resurfacing was performed, and visual analog pain scores (0 to 10) were recorded during each of 2 passes. RESULTS: Laser-assisted topical anesthesia demonstrated significantly lower mean pain scores than topical anesthesia alone. This was more pronounced during the more painful second pass. Resurfacing after laser-assisted topical anesthesia was well tolerated by 72% of subjects in pass 1 and 58% in pass 2. CONCLUSION: Laser-assisted topical anesthesia is fast, painless, and substantially more effective than conventional topical anesthesia but does not provide adequate anesthesia for full-face resurfacing in all subjects.

Adult↗