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1.  Quantitative physiology and immunohistochemistry of oral lesions 
Biomedical Optics Express  2013;4(11):2696-2709.
Angiogenesis and hypoxia are reported to correlate with tumor aggressiveness. In this study, we investigated the potential of optically measured total hemoglobin concentration (THC) and blood oxygen saturation (StO2) as a quantitative measure of angiogenesis and hypoxia in oral lesions with an immunohistochemical comparison. 12 normal subjects and 40 oral patients (22 oral squamous cell carcinoma (SCC), 18 benign/premalignant lesions including 11 verrucous hyperplasia (VH) and 7 hyperkeratosis/parakeratosis (HK)) were studied. The results showed that the THC measurement was consistent with vascular endothelial growth factor (VEGF) and microvessel staining in the stromal area, but StO2 was not associated with HIF-1α. We observed inflammation induced neovascular formation in the stromal area of VH and HK that were likely attributed to higher-than-control THC and StO2 and resulted in no difference in optical measurements between all lesions. However, we found that in majority of SCC, the ratio of THC and StO2 levels between lesions and the surrounding tissues provide potential distinguishing characteristics from VH, which are not visually differentiable from SCC, with a sensitivity, specificity, and accuracy of 91%, 68%, and 76%, respectively.
PMCID: PMC3829562  PMID: 24298427
(170.1610) Clinical applications; (170.1850) Dentistry; (170.5280) Photon migration; (300.0300) Spectroscopy
3.  Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate 
Radiation research  2010;174(3):331-340.
Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug–light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug–light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/μl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm2 significantly improved long-term tumor responses over that at 75 mW/cm2. This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm2 PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm2 PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm2 PDT provide evidence of more widespread vascular damage, which was accompanied by greater decreases in clonogenic survival. Further study of low fluence rate as a means to improve responses to PDT under conditions designed to predominantly damage vasculature is warranted.
PMCID: PMC2995951  PMID: 20726728
4.  Fluence Rate-Dependent Intratumor Heterogeneity in Physiologic and Cytotoxic Responses to Photofrin Photodynamic Therapy 
Photodynamic therapy (PDT) can lead to the creation of heterogeneous, response-limiting hypoxia during illumination, which may be controlled in part through illumination fluence rate. In the present report we consider 1) regional differences in hypoxia, vascular response, and cell kill as a function of tumor depth and 2) the role of fluence rate as a mediator of depth-dependent regional intratumor heterogeneity. Intradermal RIF murine tumors were treated with Photofrin-PDT using surface illumination at an irradiance of 75 or 38 mW/cm2. Regional heterogeneity in tumor response was examined through comparison of effects in the surface vs. base of tumors, i.e. along a plane parallel to the skin surface and perpendicular to the incident illumination. 75 mW/cm2-PDT created significantly greater hypoxia in tumor bases relative to their surfaces. Increased hypoxia in the tumor base could not be attributed to regional differences in Photofrin concentration nor effects of fluence rate distribution on photochemical oxygen consumption, but significant depth-dependent heterogeneity in vascular responses and cytotoxic response were detected. At a lower fluence rate of 38 mW/cm2, no detectable regional differences in hypoxia or cytotoxic responses were apparent, and heterogeneity in vascular response was significantly less than that during 75 mW/cm2-PDT. This research suggests that the benefits of low-fluence-rate-PDT are mediated in part by a reduction in intratumor heterogeneity in hypoxic, vascular and cytotoxic responses.
PMCID: PMC2834171  PMID: 20024165
photodynamic therapy; fluence rate; hypoxia; EF3; blood flow
5.  Mannitol Infusion Within 15 Min of Cross-Clamp Improves Living Donor Kidney Preservation 
Transplantation  2014;98(8):893-897.
Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDKs) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia experienced between the time of arterial vessel clamping and flushing the excised kidney with cold preservation solution. Damage to the tubules as a result of this cell swelling resulted in varying degrees of acute tubular necrosis (ATN) that slowed the recovery of the donor kidneys during the first 2 weeks after their transplantation.
To prevent this cell damage during LDK procurement, we changed the protocol for intravenous administration of mannitol (i.e., 12.5 or 25 g) to the donor. Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery.
OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling. An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery.
Because slow graft recovery in the first weeks after transplantation represents a risk factor for long-term graft function and survival, we believe that this change in pretreatment protocol will improve renal transplants in patients receiving LDK.
PMCID: PMC4199920  PMID: 24831920
Tubular Necrosis; Pathology; Imaging; Living donor transplantation

Results 1-5 (5)