Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens

Abstract

Background and Objectives: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/ PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. Study Design/Materials and Methods: A dorsal skinfold window chamber was installed surgically on female Sprague-Dawley rats. One milligram per kilogram of BPD solution was administered intravenously via a jugular venous catheter. Evaluated interventions were: control (no BPD, no light), PDT alone (576 nm, 16 minutes exposure time, 15 minutes post-BPD injection, 10 mm spot), PDL alone at 7 J/cm 2 (585 nm, 1.5 ms pulse duration, 7 mm spot), PDL alone at 10 J/cm 2 , PDT/PDL (PDL at 7 J/cm 2 ), and PDT/PDL (PDL at 10 J/cm 2 ). To assess changes in microvascular blood flow, laser speckle imaging was performed before, immediately after, and 18 hours post-intervention. Results: Epidermal irradiation was accomplished without blistering, scabbing or ulceration. A reduction in perfusion was achieved in all intervention groups. PDT/PDL at 7 J/ cm 2 resulted in the greatest reduction in vascular perfusion (56%). Conclusions: BPD PDT can achieve safe and selective vascular flow reduction. PDT/PDL can enhance diminution of microvascular blood flow. Our results suggest that PDT and PDT/PDL should be evaluated as alternative therapeutic options for treatment of hypervascular skin lesions including port wine stain birthmarks. Lasers Surg. Med.

Impact of velocity distribution assumption on simplified laser speckle imaging equation

“…Dunn et al [1] and Bolay et al [12] presented experimental data taken from cortical tissue with maximum C values of ~0.15. In experimental LSI data that we acquire from rodent dorsal window chamber models [15][16][17], we typically observe C values greater than 0.6 in less than 1% of the pixels (Fig. 3).…”

“…In Ref [20], the signal-to-noise ratio associated with measurement of (1/C 2 ) is given by: (16) The (S/N) rms associated with Eq. 15 is greater than .…”

“…Recently, this laser speckle imaging (LSI) method has been developed into a digital, quasi real-time technique for the mapping of blood flow [6,7]. LSI has been used to monitor noninvasively blood flow and perfusion dynamics in the brain [1,[8][9][10][11][12], retina [5,13], and skin [14][15][16][17]. We have employed LSI to monitor blood flow dynamics during photodynamic therapy [16] and have observed marked changes in the measured speckle flow index (SFI) values which is proportional to the blood flow velocity.…”

“…LSI has been used to monitor noninvasively blood flow and perfusion dynamics in the brain [1,[8][9][10][11][12], retina [5,13], and skin [14][15][16][17]. We have employed LSI to monitor blood flow dynamics during photodynamic therapy [16] and have observed marked changes in the measured speckle flow index (SFI) values which is proportional to the blood flow velocity. Cheng and Duong [18] recently proposed a simplified imaging equation that addresses a reported discrepancy [19] between the Fercher and Briers speckle imaging equation and that of Goodman [20,21].…”

Current treatment options for port wine stain birthmarks

“…In preliminary proof-ofconcept studies in a chick chorioallantoic membrane model, PDT + PDL intervention resulted in significantly more vascular damage than other study groups: 127% more than PDT (p < .01) and 47% more than PDL alone (p < .01) [6]. Further studies in a rodent dorsal skin fold model, achieved a reduction in perfusion in all intervention groups, with PDT + PDL resulting in the greatest reduction in vascular perfusion (56%) [7]. Clinical trials are on-going, but in test spots we have similarly achieved improved blanching in the PDT + PDL spots as compared to PDT or PDL alone [8].…”