Biomedical subjects

J Tulip

Publications and source records attributed to J Tulip.

At least 19 recordsLinked to original sources

PubMed2001

Light dosimetry using the P3 approximation.

In earlier work, we demonstrated that radiance, calculated using the P3 approximation in a plane wave geometry, could be used to accurately predict the optical parameters of an Intralipid/methylene blue phantom. Plane wave geometry is impractical for clinical use but the results of this work encouraged us to further develop the P3 approximation for a spherical geometry, described in this paper. Radiance predicted by this model for a defined Intralipid/methylene blue phantom was compared with radiance measured in this phantom. The results demonstrate that the spherical derivation of the P3 approximation will reproducibly predict optical parameters of a tissue phantom as effectively as the slab geometry derivation of the P3 approximation. In a similar protocol, the P3 approximation was used to estimate the optical parameters of ex vivo human prostate. Radiance in this case was measured in the prostate samples using an after loading technique. Three prostate samples tested were found to be surprisingly optically homogeneous. The after loading protocol described in this paper could form the basis of a minimally invasive and effective clinical method to optically characterize human prostate.

Humans↗

PubMed1999

Detection of transplant vasculopathy in a rat aortic allograft model by fluorescence spectroscopic optical analysis.

BACKGROUND AND OBJECTIVE: Transplant vasculopathy is a leading cause of late cardiac graft loss. We have examined laser-induced fluorescence (LIF) spectroscopy as an optical diagnostic tool for detection of intimal plaque development and inflammatory cellular invasion in a rat model of aortic allograft transplant. STUDY DESIGN/MATERIALS AND METHODS: Infrarenal aortic segments were transplanted from Lewis to Sprague Dawley rats. A range of vasculopathy development was produced by treatment with a viral anti-inflammatory protein. LIF spectra were recorded from the intima of aortic implants at 28 days. Fluorescence intensity was analyzed for correlation with vasculopathy development. RESULTS: Significant differences in LIF intensity at 400-450 nm (P < or = 0.05 by ANOVA) were detected. LIF emission was correlated with plaque growth (R2 = 0.980), vessel narrowing (R2 = 0.964), and cellular invasion (R2 = 0.971) by regression analysis. CONCLUSION: LIF optical analysis provides a nontraumatic diagnostic approach for detection of atherosclerosis prior to cardiac transplant or during development of vasculopathy after transplant.

Animals↗

PubMed1998

Radiance modelling using the P3 approximation.

Light dosimetry is an essential component of effective photodynamic therapy (PDT) of tumours. Present PDT light dosimetry techniques rely on fluence-based models and measurements. However, in a previous paper by Barajas et al, radiance-based light dosimetry was explored as an alternative approach. Although successful in demonstrating the use of Monte Carlo (MC) simulations of radiance in tissue optical characterization, the MC proved time consuming and impractical for clinical applications. It was proposed that an analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization. It has been found that the P3 approximation is one such potential solution. Radiance and fluence expressions based on the P3 approximation were used to optically characterize an Intralipid-based tissue phantom of varying concentration of scatterer (Intralipid) and absorber (methylene blue) using a plane wave illuminated, semi-infinite medium geometry. The results obtained compare favourably with the Grosjean approximation of fluence (a modified diffusion theory) using the same optical parameters (mu(a), mu(s), g). The results illustrate that radiance-based light dosimetry is a viable alternative approach to tissue characterization and dosimetry. It is potentially useful for clinical applications because of the limited number of invasive measurements needed and the speed at which the tissue can be characterized.

Data Interpretation, Statistical↗

PubMed1998

Biodistribution of Photofrin II and 5-aminolevulinic acid-induced protoporphyrin IX in normal rat bladder and bladder tumor models: implications for photodynamic therapy.

Photodynamic therapy (PDT) has been considered as a potential therapy for superficial bladder carcinomas. Cutaneous photosensitivity and reduction of bladder capacity are the two well-known complications following systemic administration of the commonly used photosensitizer, Photofrin II (PII). The objective of the present study was to evaluate whether intravesical (i.b.) instillation of photosensitizers for PDT of bladder cancer might be a more suitable treatment method. Female Fischer rats were utilized to develop orthotopic and heterotopic bladder tumor models. Rats bearing orthotopic bladder tumors were treated either intravesically or intravenously with graded doses of 5-aminolevulinic acid (ALA) or PII. Normal rats received the same doses of ALA or PII. As well, rats bearing heterotopic tumor were studied for comparison. The biodistribution times (times allowed for tissue uptake and bioconversion following drug administration) were 2, 4 or 6 h. Porphyrin fluorescence intensities within tumor, urothelium, submucosa, bladder muscularis and abdominal muscle were quantitated by confocal laser scanning microscopy. Following intravenous (i.v.) injection of ALA, tumor protoporphyrin IX (PpIX) levels peaked at 4 h and diminished by 6 h. The PpIX ratios of tumor-to-bladder mucosa, submucosa and muscle layers were 3:1, 5:1 and 8:1, respectively, 4 h following 1000 mg/kg ALA injection. After ALA instillation, the optimal biodistribution time appeared to be 4 h. Bladder instillation provided comparable tumor labeling with the i.v. route, but lost selectivity of PpIX accumulation between tumor and normal urothelium. The PpIX ratio of tumor-to-bladder muscularis was 5:1. After i.b. instillation of PII, porphyrin fluorescence was detected only within tumor and urothelium, while porphyrin fluorescence was mainly located in bladder submucosa following i.v. injection. Intravesical administration of ALA or PII might be feasible for PDT of superficial bladder cancers.

Aminolevulinic Acid↗

PubMed1997

In vivo light transmission spectra in EMT6/Ed murine tumors and Dunning R3327 rat prostate tumors during photodynamic therapy.

BACKGROUND AND OBJECTIVE: Variations in the optical coefficients in tissue and the photosensitizer during photodynamic therapy (PDT) will require adjustment of the light dose during the course of therapy. We have studied the dynamics using light transmission spectra for two different tumor models when tetrasulfonated aluminum phthalocyanine (AlPcS4) was used as photosensitizer. STUDY DESIGN/MATERIALS AND METHODS: Spectra were measured noninvasively in the EMT6/Ed murine tumor model, and with interstitially implanted source and probe fibers in the Dunning R3327-AT rat tumor model. Measurements were performed in the range 600-840 nm, using a tunable dye laser, a diode laser, and a Ti:Sapphire laser. AlPcS4 has absorption in the range 600-700 nm with an absorption peak at 670 nm in saline. RESULTS: The in vivo spectrum of AlPcS4 both in the EMT6/Ed tumor model and the Dunning R3327-AT tumor model differs from the spectrum of AlPcS4 in saline. The absorption at 670 nm was reduced, whereas the absorption at 640 nm increased. Exposure of phototherapeutic levels of light caused reduced light absorption by the photosensitizer and further spectral shift. CONCLUSION: We found that the AIPcS4 absorption spectrum changes in a biological environment, and we also observed increased light transmission at the treatment wavelength during PDT in both tumor models. Instability in the absorption spectrum of the photosensitizer may influence the effectiveness of PDT.

Animals↗

PubMed1997

Monte Carlo modelling of angular radiance in tissue phantoms and human prostate: PDT light dosimetry.

Photodynamic therapy (PDT) is a promising technique for destroying tumours. Photosensitizing drugs presently available are not sufficiently tumour specific; hence, light dosimetry is required in order to control light exposure and thereby restrict cell kill to the target tissue to avoid damage to healthy tissue. Current light dosimetry methods rely on tissue optical characterization by fluence measurements at several points. Fluence-based tissue characterization is impractical for tumours in organs such as prostate where access by optical probes is limited and the tumours are highly optically inhomogeneous. This paper explores the potential of radiance-based light dosimetry as an alternative. Correlation is found between Monte Carlo simulation of radiance in a tissue phantom and radiance measurements made using a new radiance probe. Radiance is sensitive to variations in the tissue optical parameters, absorption coefficient mu(a), scattering coefficient mu(s), and anisotropy factor g, and therefore is potentially useful for tissue characterization. Radiance measurements have several advantages over fluence measurements. Radiance measurements provide more information from a single location, better spatial resolution of the tissue optical parameters, and higher sensitivity in discriminating between different media. However, the Monte Carlo method is too slow to be of practical value for tissue characterization by correlation of measured and simulated radiance. An analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization.

Anisotropy↗

PubMed1997

Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer: progress update.

Hypocrellins are perylenequinone pigments with substantial absorption in the red spectral region and high singlet oxygen yield. They are available in pure monomeric form and may be derivatized to optimize properties of red light absorption, tissue biodistribution and toxicity. In vitro screening of synthetic derivatives of the naturally occurring compound, hypocrellin B (HB), for optimal properties of cyto-(dark) toxicity and phototoxicity resulted in selection of three compounds for preclinical evaluation: HBEA-R1 (ethanolaminated HB), HBBA-R2 (butylaminated HB) and HBDP-R1 [2-(N,N-dimethylamino)-propylamine-HB]. Extinction coefficients at 630 nm (epsilon 630) are 6230, 6190 and 4800, respectively; and 1O2 quantum yields, phi, 0.60, 0.32 and 0.42. Intracellular uptake is essentially complete within 2 h (HBEA-R1, HBBA-R2) and 20 h (HBDP-R1). Greatest uptake is associated with lysosomes and Golgi. The HBEA-R1 and HBBA-R2 elicit phototoxicity in vitro primarily via the type II mechanism, with some type I activity under stringently hypoxic conditions. Transcutaneous phototherapy with HBEA-R1 permanently ablates EMT6/Ed tumors growing in the flanks of Balb/c mice, with minimal cutaneous effects. The HBBA-R2 does not elicit mutagenic activity in strains TA98 and TA100 of Salmonella typhimurium. Further development of selected hypocrellin derivatives as photosensitizers for photodynamic therapy is warranted.

Animals↗

PubMed1996

Development of an avian model for restenosis.

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.

Angioplasty, Balloon↗

PubMed1996

Comparative study of Nd:YAG laser angioplasty at 1.06 microns, 1.32 microns, and 1.44 microns wavelengths: decreased vascular spasm and early mortality with 1.44 microns laser ablation.

BACKGROUND AND OBJECTIVE: Although laser angioplasty has been demonstrated to be effective for the treatment of long, complex coronary arterial atherosclerotic stenoses, there is an associated risk of acute arterial spasm, dissection, and perforation as well as a significant restenosis rate. It has been postulated that the use of lasers emitting at wavelengths designed for radiation absorption by water would decrease local tissue trauma. STUDY DESIGN/MATERIALS AND METHODS: We have examined the use of a Nd:YAG laser designed to emit at 1.44 microns, an absorption peak for water, and compared the results of laser ablation at 1.06 microns, 1.32 microns, and 1.44 microns wavelengths. Nd:YAG laser angioplasty was performed in the abdominal aorta of White Leghorn roosters. Acute and chronic vascular trauma was assessed by contrast angiography and histological analysis. RESULTS: There was a significant decrease in early mortality with 1.44 microns laser ablation. This decreased mortality after 1.44 microns ablation was associated with a decrease in vascular spasm, perforation, and thermal damage. Atherosclerotic plaque development at follow up was decreased with 1.44 microns ablation but this was not significant. CONCLUSION: 1.44 microns laser ablation decreases early vascular trauma and mortality and may decrease subsequent atherosclerotic plaque development.

Angiography↗

PubMed1996

Anisotropy of radiance in tissue phantoms and Dunning R3327 rat tumors: radiance measurements with flat cleaved fiber probes.

BACKGROUND AND OBJECTIVE: The goal of this study is to determine if flat cleaved fiber probes are appropriate for interstitial measurements of radiance in tissue. Flat cleaved probes have the advantage of high responsivity, and they are easy to insert into tissue. Owing to the non-isotropic response of flat cleaved probes, a calibration function is required, taking the anisotropy in the radiance in tissue into account. STUDY DESIGN, MATERIALS AND METHODS: The method used to determine this function consists of radiance measurements in tissue, performed with a flat cleaved fiber probe mounted on a stereotactic stage for insertion into the tissue from different directions. Interstitial irradiation at 630 nm was delivered by a spherical source. RESULTS: We found that the degree of anisotropy in the radiance decreases with increasing distance from the interstitially implanted source in two different tissue phantoms and in the Dunning R3327-AT and R3327-H rat tumor models. CONCLUSION: A position-dependent calibration function is required for interstitially implanted flat cleaved fiber probes. An anisotropy function is presented, which modifies the measurements of radiance with a flat cleaved probe, to account for the change in anisotropy in the radiance. The anisotropy functions for the two tumor models differ substantially.

Animals↗

PubMed1996

Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study.

Hypocrellin compounds were selected as potential photosensitizers for photodynamic therapy (PDT) owing to their high quantum yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light absorption in the red spectral region, among other properties. Parent hypocrellins A and B share an absorption peak at 658 nm. These molecules may therefore be considered useful progenitors of derivatives which absorb more strongly in the red, considering that the ideal sensitizer should absorb in the 650-800 nm range, beyond the absorption range of hemoglobin and melanin, and where light penetration in tissues is maximized through reduced scattering. A series of pure, monomeric hypocrellin derivatives was tested for properties of dark cytotoxicity and photosensitizing potential by clonogenic assay in monolayer cultures of EMT6/Ed murine tumor cells. Their respective toxicities are reported on a molar basis. The in vitro screening assay has, to date, resulted in the selection of four hypocrellin derivatives for further development as photosensitizers for PDT. Cellular uptake for photosensitizing doses of selected compounds was determined by fluorimetry. Dose escalation studies in rodents indicate that potentially photosensitizing doses promote no demonstrable systemic toxicity.

Animals↗

PubMed1996

Photosensitization by anticancer agents 21: new perylene- and aminonaphthoquinones.

Hypocrellins are under intensive investigation as photosensitizing agents for photodynamic therapy (PDT). A recent advance in the synthesis of hypocrellin congeners resulted in the production of an amino-substituted hypocrellin-B, and its "half chromophore." Both compounds exhibit stronger red light absorption than previously reported hypocrellins, and, therefore, merit investigation as photosensitizers.

Animals↗

PubMed1995

Laser-induced fluorescence: III. Quantitative analysis of atherosclerotic plaque content.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence (LF) spectroscopic analysis of the chemical composition of atherosclerotic plaque was examined. STUDY DESIGN/MATERIALS AND METHODS: The intima of 18 dog aortas was injected with chemical compounds found in atherosclerotic plaque. Spectra were recorded in air prior to and after injection of collagens I, III and IV, elastin, cholesterol, triglyceride, and beta-nicotinamide adenine dinucleotide (NADH). RESULTS: Significant changes in LF intensity were detected after injection of collagens I and III, cholesterol and elastin in thoracic aorta (P < 0.001), but not with triglyceride or NADH. Minor changes were detected in abdominal aorta. Multiple regression analysis of LF intensity ratios demonstrated a clear correlation with the quantity of injected collagens I (R2 = 0.90-0.99) and III (R2 = 0.84-1.0), cholesterol (R2 = 0.72-0.76), and triglyceride (R2 = 0.68-0.80) in both thoracic and abdominal aorta. The correlation between LF and atherosclerotic plaque composition was confirmed in a rooster model of atherosclerosis where multiple regression analysis predicted the measured aortic cholesterol (R2 = 0.78) and triglyceride content (R2 = 0.96). CONCLUSIONS: (1) Fluorescence spectra recorded from dog aorta were significantly altered by injection of collagens I and III, cholesterol, and elastin. (2) LF may allow quantitative assessment of plaque chemical content.

Analysis of Variance↗

PubMed1995

Uptake kinetics and intracellular localization of hypocrellin photosensitizers for photodynamic therapy: a confocal microscopy study.

Hypocrellins are naturally occurring compounds with photosensitizing properties in biological systems. We have prepared synthetic derivatives of hypocrellin B, which have promise as photosensitizers in the clinical application of photodynamic therapy. The intracellular localization and uptake kinetics of hypocrellin B and several selected hypocrellin congeners were determined semiquantitatively by fluorescence confocal microscopy in monolayer cultures of EMT6/Ed murine tumor cells. Each compound had unique uptake kinetics. Although no compound tested to date has demonstrated nuclear labeling, most could be detected in lysosomes, Golgi, endoplasmic reticulum and, to a minor extent, in cellular membranes. No two compounds gave identical labeling distributions. The differences are assumed to originate in physicochemical properties characteristic of each compound, which may ultimately impact upon the primary modality of phototoxicity.

Animals↗

PubMed1993

Laser induced fluorescence identification of sinoatrial and atrioventricular nodal conduction tissue.

UNLABELLED: Transcatheter ablation of nodal tissue is used for the treatment of arrhythmia resistant to medical therapy. We have investigated the use of laser induced fluorescence spectroscopy for the in vitro recognition of nodal conduction tissue. Twelve fresh human necropsy specimens (< 48 hours) were obtained from sinoatrial node and atrioventricular node areas. Spectra were recorded during excitation at 308 nm (XeCl excimer laser, 1.5-2.0 mJ/pulse, 10 Hz). Ech area examined was marked for subsequent histologic examination. Four hundred eleven spectra were obtained, of which 37 contained nodal conduction tissue (21 sinoatrial, 16 atrioventricular node). Normalized fluorescence emission intensity from these areas was compared with that of surrounding endomyocardial tissue at 18 wavelengths and 35 ratios of fluorescence intensity at selected wavelengths. Spectra recorded from nodal tissue could be clearly distinguished by a visible decrease in fluorescence emission intensity at wavelengths from 440 to 500 nm (P < 0.0006 at 450 nm), peak area, and peak width when compared to that of adjacent atrial endomyocardial tissue. Nodal conduction tissue was also distinguished from ventricular endocardium (14 spectra) by an increase in fluorescence emission at 430 to 550 nm (P < 0.0001). The specificity was 73% and 88% and the sensitivity was 73% and 60% for sinus nodal and atrioventricular nodal conduction tissue identification, respectively. A ratio of fluorescence emission intensity > 1.3 for 380/475 nm was able to detect nodal conduction tissue (P < 0.001). CONCLUSION: Laser induced fluorescence can differentiate nodal conduction tissue from atrial and ventricular endocardium and may provide a new diagnostic tool for the recognition and subsequent ablation of nodal conduction tissue.

Adolescent↗

PubMed1993

Optical properties of experimental prostate tumors in vivo.

The optical properties of tumor tissue provide important information for optimizing treatment plans in photodynamic therapy, especially when interstitial application by multiple fibers is planned. Near infrared light, required to activate novel photosensitizers, should facilitate improved light penetrance of tumor tissue compared with 630 nm light used for activating Photofrin II. We have measured light energy fluence rates for 630 and 789 nm light along radial tracks from a single laterally diffusing optical fiber centrally implanted into Dunning R3327-AT and R3327-H rat prostate tumors in anesthetized rats. A total of 20 R3327-AT and 10 R3327-H tumors were used in this study with volumes from 2.6 to 13.3 cm3. Light track data were analyzed by an empirical model that described light attenuation. At 630 nm, light attenuation coefficients (LAC) were approximately 1.9 x higher than those at 789 nm for both tumors with the well-differentiated, well-perfused tumor (R3327-H) attenuating to a greater extent than did the rapidly growing anaplastic tumor (R3327-AT). The intertumor variation of LAC was greater than the spatial variations observed within individual tumors. LAC were a function of tumor volume for only 630 nm light in the R3327-AT tumors.

Animals↗

PubMed1992

Analysis of tissue optical coefficients using an approximate equation valid for comparable absorption and scattering.

New photosensitizers activated by longer wavelengths than 630 nm light used with Photofrin II are under evaluation by various groups for the treatment of malignancies. Any increase in tumour volume destroyed by these agents as compared to Photofrin II will be partly determined by tissue penetrance at the longer wavelengths. Attenuation coefficients were measured for various tissues at 630 nm and the more penetrative near infrared wavelength of 789 nm. A new model of light propagation in tissue is shown to be accurate for arbitrary ratios of absorption and scattering, by comparison with a rigorous solution to the transport equation. Absorption and transport scattering coefficients of tissues at 630 and 789 nm were obtained by fitting this model to optical attenuation measurements. In vitro tissues included bovine heart, kidney and tongue, pig liver and fat, and chicken muscle; in vivo tissues included Dunning R3327-AT and R3327-H tumours. The penetration depth was found to be 1.35-2.25 times greater at 789 than 630 nm, depending on tissue type. The greatest differences in penetration between the two wavelengths were in the highly pigmented tissues. These substantial increases in penetration in the infrared may be important in future applications of photodynamic therapy.

Absorption↗

PubMed1991

Laser-induced fluorescence emission: I. The spectroscopic identification of fibrotic endocardium and myocardium.

UNLABELLED: Laser-induced fluorescence has been developed as a guidance system for laser angioplasty. Laser ablation has been used for resection of arrhythmogenic ventricular scar. We have investigated the use of laser-induced fluorescence for the detection of fibrotic and ischemic changes in endocardium and myocardium. Fluorescence emission spectra from human necropsy specimens were correlated with histologic examination. Normalized fluorescence intensity detected from both the endocardial and the myocardial surfaces of the fibrotic ventricular specimens was significantly higher than that of corresponding normal specimens at 440 to 475 nm. Fibrotic endocardium could be identified by a fluorescence emission intensity ratio less than 1.5 for wavelength ratio 375/450nm. Acutely infarcted endocardium was recognizable by a ratio of 1.5 to 2.0. The specificity and sensitivity of detection of scarred endocardium was 70 and 100%, respectively. Fibrotic myocardium was also consistently identified by fluorescence spectroscopy. CONCLUSION: Fluorescence emission spectroscopy can differentiate normal and fibrotic endocardium and myocardium, in vitro. This technique may be useful for guidance during laser ablation of arrhythmogenic ventricular scar.

Capillaries↗