Flow field study of radiofrequency ablation of renal sympathetic nerve: Numerical simulation and PIV experiments.

Renal sympathetic denervation (RSD) is a new method for the treatment of resistant hypertension (RH). However, few studies have focused on the effects of RSD on blood flow and the interaction between temperature field and flow field. In this paper, firstly, we designed a numerical simulation of electromagnetic field, flow field and temperature field coupling by finite element method. Secondly, numerical simulation results were verified by particle image velocimetry (PIV) and vitro experiment. From the simulation results, when the flow velocity increases to 0.05 m/s, the turbulence near the electrode disappeared and flow state became uniform laminar flow. With the increases of flow velocity (0 m/s to 0.1 m/s), temperature rise of the renal artery, the electrode tip and blood decreased from 13°C, 24°C and 5.4°C to 9.3°C, 9.7°C and 0.2°C, respectively. From PIV experiment and vitro experiment results, when the flow rate increases to 0.5 L/min, it appeared similar phenomenon with the velocity of 0.05 m/s in simulation. With the increases of flow rate (0 L/min to 0.8 L/min), temperature rise of three points decreased from 11.2°C, 20.5°C and 3.6°C to 7.8°C, 8.5°C, and 0.4°C, respectively. When the blood flow rate exceeds 0.5 L/min, there is no large velocity gradient and reflux area in the flow field, so there will be no hemolysis and thrombosis. Therefore, the temperature field has less influence on the flow field. With the increase of flow rate, the temperature at all three points decreases. Therefore, the flow field has an effect on the temperature field. But the central temperature of renal artery can still reach the treatment target in which temperature rises to be more than 6°C. Therefore, this study preliminarily verified the safety and effectiveness of RSD.

Temperature elevation in the human brain and skin with thermoregulation during exposure to RF energy.

BACKGROUND: Two international guidelines/standards for human protection from electromagnetic fields define the specific absorption rate (SAR) averaged over 10 g of tissue as a metric for protection against localized radio frequency field exposure due to portable devices operating below 3-10 GHz. Temperature elevation is suggested to be a dominant effect for exposure at frequencies higher than 100 kHz. No previous studies have evaluated temperature elevation in the human head for local exposure considering thermoregulation. This study aims to discuss the temperature elevation in a human head model considering vasodilation, to discuss the conservativeness of the current limit. METHODS: This study computes the temperature elevations in an anatomical human head model exposed to radiation from a dipole antenna and truncated plane waves at 300 MHz-10GHz. The SARs in the human model are first computed using a finite-difference time-domain method. The temperature elevation is calculated by solving the bioheat transfer equation by considering the thermoregulation that simulates the vasodilation. RESULTS: The maximum temperature elevation in the brain appeared around its periphery. At exposures with higher intensity, the temperature elevation became larger and reached around 40 °C at the peak SAR of 100 W/kg, and became lower at higher frequencies. The temperature elevation in the brain at the current limit of 10 W/kg is at most 0.93 °C. The effect of vasodilation became notable for tissue temperature elevations higher than 1-2 °C and for an SAR of 10 W/kg. The temperature at the periphery was below the basal brain temperature (37 °C). CONCLUSIONS: The temperature elevation under the current guideline for occupational exposure is within the ranges of brain temperature variability for environmental changes in daily life. The effect of vasodilation is significant, especially at higher frequencies where skin temperature elevation is dominant.

Skin thermophysiological effects of 448 kHz capacitive resistive monopolar radiofrequency in healthy adults: A randomised crossover study and comparison with pulsed shortwave therapy.

Radiofrequency-based electrophysical agents (EPA) have been used in therapy practice over several decades (e.g., shortwave therapies). Currently, there is insufficient evidence supporting such devices operating below shortwave frequencies. This laboratory-based study investigated the skin physiological effects of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) and compared them to pulsed shortwave therapy (PSWT). In a randomised crossover study, seventeen healthy volunteers received four treatment conditions - High, Low and Placebo dose conditions receiving 15-min CRMRF treatment and a Control condition receiving no intervention. Fifteen participants also received high dose PSWT for comparison. Treatment was applied to the right lower medial thigh. Pre, post and 20-min follow-up measurements of skin temperature (SKT), skin blood flow (SBF) and nerve conduction velocity (NCV) were obtained using Biopac MP150 system. Group data were compared using the ANOVA model. Statistical significance was set at p ≤ 0.05 (0.8P, 95%CI). Significant increase and sustenance of SKT with both high and low dose CRMRF was demonstrated over the other groups (p < 0.001). PSWT increased SKT significantly (p < 0.001) but failed to sustain it over the follow-up. However, among the five conditions, only high dose CRMRF significantly increased and sustained SBF (p < 0.001). Overall, the CRMRF physiological responses were significantly more pronounced than that of PSWT. No significant changes in NCV were noted for any condition. Physiological changes associated with CRMRF were more pronounced when compared to PSWT, placebo or control. Any potential stronger therapeutic benefits of CRMRF need to be confirmed by comparative clinical studies.

Effects of far infrared therapy on arteriovenous fistulas in hemodialysis patients: a meta-analysis.

BACKGROUND: Far infrared (FIR) therapy may have a beneficial effect on maturity and function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this pooled analysis to assess the protective effects of FIR therapy in HD patients. METHODS: The randomized controlled trials (RCTs) and quasi-RCTs of FIR therapy for HD patients were searched from multiple databases. Relevant studies were screened according to the predefined inclusion criteria. The meta-analyses were performed using RevMan 5.2 software (The Cochrane Collaboration, Oxford, UK). RESULTS: Meta-analysis showed that FIR therapy could significantly increase the vascular access blood flow level (MD, 81.69 ml/min; 95% CI, 46.17-117.21; p < .001), AVFs diameter level (MD, 0.36 mm; 95% CI, 0.22-0.51; p < .001), and the primary AVFs patency (pooled risk ratio = 1.24; 95% CI, 1.12-1.37, p < .001). In addition, therapy with FIR ray radiation could decrease AVFs occlusion rates (pooled risk ratio = 0.20; 95% CI, 0.08-0.46; p < .001) and the level of needling pain (pooled risk ratio = 0.08; 95% CI, 0.06-0.10, p < .001). CONCLUSIONS: FIR therapy can reduce AVFs occlusion rates and needling pain level, while significantly improve the level of vascular access blood flow, AVFs diameter and the primary AVFs patency.

Review of temperature dependence of thermal properties, dielectric properties, and perfusion of biological tissues at hyperthermic and ablation temperatures.

The application of supraphysiological temperatures (>40°C) to biological tissues causes changes at the molecular, cellular, and structural level, with corresponding changes in tissue function and in thermal, mechanical and dielectric tissue properties. This is particularly relevant for image-guided thermal treatments (e.g. hyperthermia and thermal ablation) delivering heat via focused ultrasound (FUS), radiofrequency (RF), microwave (MW), or laser energy; temperature induced changes in tissue properties are of relevance in relation to predicting tissue temperature profile, monitoring during treatment, and evaluation of treatment results. This paper presents a literature survey of temperature dependence of electrical (electrical conductivity, resistivity, permittivity) and thermal tissue properties (thermal conductivity, specific heat, diffusivity). Data of soft tissues (liver, prostate, muscle, kidney, uterus, collagen, myocardium and spleen) for temperatures between 5 to 90°C, and dielectric properties in the frequency range between 460 kHz and 3 GHz are reported. Furthermore, perfusion changes in tumors including carcinomas, sarcomas, rhabdomyosarcoma, adenocarcinoma and ependymoblastoma in response to hyperthmic temperatures up to 46°C are presented. Where appropriate, mathematical models to describe temperature dependence of properties are presented. The presented data is valuable for mathematical models that predict tissue temperature during thermal therapies (e.g. hyperthermia or thermal ablation), as well as for applications related to prediction and monitoring of temperature induced tissue changes.

Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free hemodialysis access patency of recurrent obstructive lesions.

OBJECTIVE: To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA). METHODS: This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached. RESULTS: Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02). CONCLUSIONS: This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA.

Qualitative bone CT as a tool to assess vascularization in irradiated bone: an animal study.

OBJECTIVE: The purpose of this paper was to find a correlation between laser doppler flowmetry (LDF) and the bone mineral density quotient (BMDQ) to evaluate irradiated bone quality preoperatively. MATERIALS AND METHODS: Premolars and molars were extracted from six minipigs. After a three-month healing period, three animals received irradiation at a total dose of 24 Gy. Three months after irradiation, quantitative computed tomography was performed using a calibration bone phantom to determine the 120-position BMDQ in the alveolar bone. A drill template was created to define the exact location for measurement. LDF was then recorded after osteotomy of the residual alveolar ridge. The correlation between the BMDQ and LDF was investigated. RESULTS: There was a linear negative correlation between LDF and BMDQ in non-irradiated bone (r = -0.435, P = 0.001) and less pronounced also in irradiated bone (r = -0.309, P = 0.017). In both non-irradiated and irradiated bone, we found distinct differences between the maxilla and mandible with respect to BMDQ. However, a clear difference in mandibular and maxillary vascularity was only seen in non-irradiated bone. CONCLUSION: In non-irradiated bone, LDF and BMDQ were inversely correlated. In irradiated bone, the BMDQ alone is not an adequate preoperative tool for evaluating bone quality because it was not correlated with bone perfusion.

Microbubble and ultrasound radioenhancement of bladder cancer.

BACKGROUND: Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation. METHODS: Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals). RESULTS: Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation. CONCLUSION: Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death.

Preclinical in vivo evaluation of NPe6-mediated photodynamic therapy on normal vasculature.

BACKGROUND AND OBJECTIVE: Current treatments of port-wine stain birthmarks typically involve use of a pulsed dye laser (PDL) combined with cooling of the skin. Currently, PDL therapy protocols result in varied success, as some patients experience complete blanching, while others do not. Over the past decade, we have studied the use of photodynamic therapy (PDT) as either a replacement or adjuvant treatment option to photocoagulate both small and large vasculature. The objective of the current study was to evaluate a PDT protocol that involves use of an alternate intravascular photosensitizer mono-L-aspartylchlorin-e6 (NPe6) activated by an array of low-cost light emitting diodes. STUDY DESIGN/MATERIALS AND METHODS: To monitor the microvasculature, a dorsal window chamber model was installed on 22 adult male mice. The light source consisted of a custom-built LED array that emitted 10 W at a center wavelength of 664 nm (FWHM = 20 nm). The light source was positioned at a fixed distance from the window chamber to achieve a fixed irradiance of 127 mW/cm(2). A retroorbital injection of NPe6 (5 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose-response experimental design to evaluate the efficacy of NPe6-mediated PDT. RESULTS: We observed three general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed an acute decrease in blood flow followed by gradual restoration of blood flow over the 7-day monitoring period; and (3) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period. Dose-response analysis enabled identification of 85 J/cm(2) as a characteristic radiant exposure required to achieve persistent vascular shutdown at Day 7 following PDT. CONCLUSION: The experimental data suggest that NPe6-mediated PDT can achieve persistent vascular shutdown of normal microvasculature.

Noninvasive cutaneous blood flow as a response predictor for visible light therapy on segmental vitiligo: a prospective pilot study.

BACKGROUND: Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy. OBJECTIVES: To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV. METHODS: Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period. RESULTS: The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes. CONCLUSIONS: Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.

Side effects of radiation in musculoskeletal oncology: clinical evaluation of radiation-induced fractures.

Radiation therapy and chemotherapy, while they remain an essential part of the multidisciplinary treatment of cancers, they have led to unwanted complications. Radiation-induced complications include wound and bone, growth, nervous system, tumorigenic, lung, gastrointestinal, hepatic and other complications. In this article we review the side effects of radiation therapy in musculoskeletal oncology emphasizing on bone, present our long experience, and discuss the current literature regarding radiation-induced bone complications and their management and outcome.

The diabetic foot and leg: combined He-Ne and infrared low-intensity lasers improve skin blood perfusion and prevent potential complications. A prospective study on 30 Egyptian patients.

The objective of this study was to examine skin blood flow in diabetic patients having disease-related skin lesions, and to evaluate possible improvement imposed by low-intensity laser therapy (LILT) as a new treatment modality. Thirty patients (in addition to 15 controls receiving conventional treatment = group II and 15 others receiving no treatment = group III) having diabetes-related skin lesions were tested for skin blood flow by laser Doppler flowmetry. Group I patients received LILT by a specified dosimetry. This was by combined uniform He-Ne and infrared lasers delivered by a scanner over the affected area. This study used a paired t test to determine the significance of blood flow recovery after treatment within each group while Independent t test compared results between the three groups. The level of significance was p < 0.05. The most frequently detected diabetes specific skin lesions were dryness, nail changes, hair loss, infections, itching, and frank eczema-like reactions, mostly in combinations (76%). This pattern appears specific for Egyptians as it is different from data registered in foreign literature. The minimum perfusion flow improved from 16.45 before LILT to 25.94 after, while maximum flow recovered from 32.91 to 48.47 and basal perfusion changed from 24.68 to 34.84 blood perfusion units. The percentage change in perfusion values was 23.17. All these were statistically significant. The study demonstrates that diabetes-linked skin lesions have a special pattern in Egyptians and are apparently caused by deranged skin blood flow .The deficit is measurable by laser flowmetry and can be partially reversed by LILT.

[The use of ozone and low-intensive laser irradiation in complex treatment of complicated duodenal ulcer].

The study is based on the examination of 12 patients with perforative duodenal ulcer and 24 patients operated on recurrent bleeding duodenal ulcer. Some component of the immune system, such as T- and B-lymphocytes rates, immunoglobulin rate and macrophagal activity, were decreased prior the beginning of the complex treatment. Normalisation of humoral and cell immunity was registered on 10-12 days after the beginning of the ozone and low-intensive laser irradiation.

[Method of local treatment of trophic ulcers of venous etiology].

The study is based on the results of local treatment of trophic ulcers of 150 patients with chronic venous insufficiency of the lower extremities. Local treatment is laser treatment and diagnostic unit with a wavelength λ=0,65 mkm and output power of 30 mW in pulsed mode for 10 minutes 1 times per day for 7-10 days. As an objective criterion for determining the speed and intensity of the healing of trophic ulcers and non-contact fixing their area of applied computer thermography. True healing of ulcers was achieved in all patients during the period from 14 to 28 days.

Tumour perfusion assessment during regional hyperthermia treatment: comparison of temperature probe measurement with H(2)(15)O-PET perfusion.

PURPOSE: Hyperthermia treatment might increase tumour oxygenation and perfusion, as has been reported for experimental tumours. The present study was performed to investigate this hypothesis in patients undergoing regional hyperthermia treatment. METHODS: Thirteen patients with primary or recurrent pelvic tumours were included in this study. Prior to and up to one hour after regional hyperthermia, perfusion was quantitatively determined by H(2)(15)O-PET. The fused CT-PET images were used to extract tumour time-activity curves and to identify the catheter position. Perfusion was calculated from the total tumour time-activity curves and for the time-activity curves at the catheter site. Additionally, perfusion was calculated from the temperature-time curves measured using temperature probes. RESULTS: Perfusion values calculated using H(2)(15)O-PET and those deduced from temperature probe measurements are significantly correlated with a correlation coefficient, R = 0.21. The perfusion values deduced from the temperature measured in a body cavity do not provide information about average tumour perfusion. Perfusion values deduced from the temperature are overestimated for very poorly perfused tissues and underestimated for highly perfused tissues. CONCLUSIONS: Temperature measurement during hyperthermia may allow only determination of intermediate perfusion values.

[Use of alternating magnetic field with the frequency of spontaneous local vessels oscillation for rehabilitation of patients after dental implantation].

New software-hardware system for diagnostic and treatment (RF patents: number 75294, 2008 and number 75314, 2008) allowing to use the technique of microcirculatory bed regional pulse vessels control (RF patent number 2383369, 2008) for optimization of patients' rehabilitation process after dental implantation operation. It was shown the normalizing action of alternating magnetic field with the frequency of spontaneous local vessels oscillation by comparison of regional blood flow indices.

Evaluating the Far-Infrared Radiation Bioeffects on Micro Vascular Dysfunction, Nervous System, and Plantar Pressure in Diabetes Mellitus.

The most frequent clinical complication is diabetes. Diabetes is characterized by elevated blood glucose levels resulting in sensory nerve damage or lesions. Diabetic foot wounds are often slow to heal and require medical attention and monitoring. This study evaluates the effect of far-infrared radiation on the microcirculation and plantar pressure in the diabetic foot. Ten diabetics and 4 nondiabetics were recruited in this study. The diabetic group was examined before and after the intervention in each month for 3 consecutive months. Four nondiabetic groups were also measured before and after the intervention for 2 weeks in each month. The surface temperature and blood flow in the diabetic foot was significantly improved (temperature: 32.1 ± 2.3°C vs 33.5 ± 2.2°C, P < .05; blood flow image: 118.3 ± 58.1 PU [perfusion unit] vs 50.4 ± 4.3 PU, P < .05). The sympathetic nerve activity index LF also increased from 40.8 ± 18.6% to 61.8 ± 13.5% (P = .07) in the second month. Plantar pressure tended to increase in the third month. This might indicate that far-infrared radiation could affect the mechanical properties of the plantar foot soft tissue. These results indicated that the effects of far-infrared radiation would improve blood circulation and change the soft tissue properties in the diabetic foot.

Microwaves induce peripheral vasodilation squirrel monkeys.

Vasomotor activity in cutaneous tail veins was indexed by changes in local skin temperature during exposure of the whole body to 12.3-centimeter continuous microwaves. At an ambient temperature (26 degrees C) just below that at which tail vessels normally vasodilate, criterion dilation was initiated by 5-minute exposures to a microwave power density of 8 milliwatts per square centimeter. This intensity deposits energy equivalent to approximately 20 percent of the monkey's resting metabolic rate but produces no observable change in deep body temperature. Intensity increments of 3 to 4 milliwatts per square centimeter for 1 degree C reductions in ambient temperature below 26 degrees C produced identical responses. That no vasodilation occurred during infrared exposures of equivalent power density suggests that noncutaneous thermosensitive structures may mediate microwave activation of thermoregulatory responses in the peripheral vasomotor system.

Blood flow dynamics after laser therapy of port wine stain birthmarks.

BACKGROUND AND OBJECTIVE: During laser therapy of port wine stain (PWS) birthmarks, regions of perfusion may persist. We hypothesize that such regions are not readily observable even when laser surgery is performed by highly experienced clinicians. The objective of this study was to use objective feedback to assess the acute vascular response to laser therapy. STUDY DESIGN/MATERIALS AND METHODS: A clinic-friendly laser speckle imaging (LSI) instrument was developed to provide the clinician with real-time images of blood flow during laser therapy. Images were acquired from patients undergoing laser therapy of PWS birthmarks at Scripps Clinic and the Beckman Laser Institute and Medical Clinic. Blood flow maps were extracted from the acquired imaging data. Histogram-based analysis was applied in grading the degree of heterogeneity present in the blood flow maps after laser therapy. RESULTS: Collectively, two types of patient responses were observed in response to laser exposure: (1) an immediate increase in perfusion within minutes after laser therapy; and (2) an overall decrease in blood perfusion approximately 1 hour after laser therapy, with distinct regions of persistent perfusion apparent in the majority of post-treatment blood-flow images. A comparison of blood flow in PWS and adjacent normal skin demonstrated that PWS blood flow can be greater than, or sometimes equivalent to, that of normal skin. CONCLUSION: In general, a decrease in skin perfusion is observed during pulsed laser therapy of PWS birthmarks. However, a heterogeneous perfusion map was frequently observed. These regions of persistent perfusion may be due to incomplete photocoagulation of the targeted vessels. We hypothesize that immediate retreatment of these regions identified with LSI, will result in enhanced removal of the PWS vasculature. Lasers Surg. Med. 41:563-571, 2009. (c) 2009 Wiley-Liss, Inc.

Simulations of measured photobleaching kinetics in human basal cell carcinomas suggest blood flow reductions during ALA-PDT.

BACKGROUND AND OBJECTIVE: In a recently completed pilot clinical study at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma (sBCC) received topical application of 20% 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm(-2). Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by fluorescence spectroscopy. In most cases, the rate of bleaching slowed as treatment progressed, leaving a fraction of the PpIX unbleached despite sustained irradiation. To account for this feature, we hypothesized a decrease in blood flow during ALA-photodynamic therapy (PDT) that reduced the rate of oxygen transported to the tissue and therefore attenuated the photobleaching process. We have performed a detailed analysis of this hypothesis. STUDY DESIGN/MATERIALS AND METHODS: We used a comprehensive, previously published mathematical model to simulate the effects of therapy-induced blood flow reduction on the measured PpIX photobleaching. This mathematical model of PDT in vivo incorporates a singlet-oxygen-mediated photobleaching mechanism, dynamic unloading of oxygen from hemoglobin, and provides for blood flow velocity changes. It permits simulation of the in vivo photobleaching of PpIX in this patient population over the full range of irradiances and fluences. RESULTS: The results suggest that the physiological equivalent of discrete blood flow reductions is necessary to simulate successfully the features of the bleaching data over the entire treatment fluence regime. Furthermore, the magnitude of the blood flow changes in the normal tissue margin and lesion for a wide range of irradiances is consistent with a nitric-oxide-mediated mechanism of vasoconstriction. CONCLUSION: A detailed numerical study using a comprehensive PDT dosimetry model is consistent with the hypothesis that the observed trends in the in vivo PpIX photobleaching data from patients may be explained on the basis of therapy-induced blood flow reductions at specific fluences.