Biomedical subjects

Timothy C Zhu

Publications and source records attributed to Timothy C Zhu.

18 recordsLinked to original sources

PubMed2006

Measurement of in-air output ratios using different miniphantom materials.

In-air output ratios, S(c), were measured using miniphantoms made of PMMA (thickness 2.4-24 g cm(-2)), graphite (1.8-26.5 g cm(-2)), copper (1.6-23.3 g cm(-2)) and lead (2.3-21.6 g cm(-2)), for collimator settings of 3 x 3 to 40 x 40 cm(2), and x-ray energies of 6 MV and 15 MV, respectively. The effects of the miniphantom on S(c) were quantified as correction factors as functions of collimator setting, material types and miniphantom thickness for each photon energy to correct the measured values. For miniphantoms with sufficient thickness to eliminate electron disequilibrium, the total correction factors can be expressed as multiplications of three factors: the attenuation correction factor, the mass energy absorption correction factor and the phantom scatter correction factor. This formalism implies that the collimator setting dependence of the correction factor is mainly caused by the energy spectrum shift. The narrow-beam attenuation coefficients in various phantom materials for different collimator settings were determined in narrow-beam geometries using a specially constructed collimator mounted on the tray holder of the accelerator. We have determined that the maximum total correction factor is approximately 1.01. For miniphantoms made of PMMA, graphite, copper and lead, at the miniphantom thickness of 10 g cm(-2), the maximum total correction factors are 1.002, 1.003, 1.005, 1.007, and 1.002, 1.003, 1.008 and 1.009 for 6 MV and 15 MV, respectively.

Air↗

PubMed2006

Updated results of a phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients with locally recurrent prostate cancer.

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.

Adenocarcinoma↗

PubMed2005

A method for determination of the absorption and scattering properties interstitially in turbid media.

We have developed a method to quickly determine tissue optical properties (absorption coefficient mu(a) and transport scattering coefficient mu'(s)) by measuring the ratio of light fluence rate to source power along a linear channel at a fixed distance (5 mm) from an isotropic point source. Diffuse light is collected by an isotropic detector whose position is determined by a computer-controlled step motor, with a positioning accuracy of better than 0.1 mm. The system automatically records and plots the light fluence rate per unit source power as a function of position. The result is fitted with a diffusion equation to determine mu(a) and mu'(s). We use an integrating sphere to calibrate each source-detector pair, thus reducing uncertainty of individual calibrations. To test the ability of this algorithm to accurately recover the optical properties of the tissue, we made measurements in tissue simulating phantoms consisting of Liposyn at concentrations of 0.23, 0.53 and 1.14% (mu'(s) = 1.7-9.1 cm(-1)) in the presence of Higgins black India ink at concentrations of 0.002, 0.012 and 0.023% (mu(a) = 0.1-1 cm(-1)). For comparison, the optical properties of each phantom are determined independently using broad-beam illumination. We find that mu(a) and mu'(s) can be determined by this method with a standard (maximum) deviation of 8% (15%) and 18% (32%) for mu(a) and mu'(s), respectively. The current method is effective for samples whose optical properties satisfy the requirement of the diffusion approximation. The error caused by the air cavity introduced by the catheter is small, except when mu(a) is large (mu(a) > 1 cm(-1)). We presented in vivo data measured in human prostate using this method.

Absorption↗

PubMed2005

Optimized interstitial PDT prostate treatment planning with the Cimmino feasibility algorithm.

The primary aim of this study was to determine whether optimized photodynamic therapy (PDT) treatment planning (seeking optimized positions, lengths, and strengths of the light sources to satisfy a given dose prescription) can improve dose coverage to the prostate and the sparing of critical organs relative to what can be achieved by the standard PDT plan. The Cimmino algorithm and search procedures based on that algorithm were tested for this purpose. A phase I motexafin lutetium (MLu)-mediated photodynamic therapy protocol is ongoing at the University of Pennsylvania. PDT for the prostate is performed with cylindrical diffusing fibers of various lengths inserted perpendicular to a base plate to obtain longitudinal coverage by a matrix of parallel catheters. The standard plan for the protocol uses sources of equal strength with equal spaced (1-cm) loading. Uniform optical properties were assumed. Our algorithms produce plans that cover the prostate and spare the urethra and rectum with less discrepancy from the dose prescription than the standard plan. The Cimmino feasibility algorithm is fast enough that changes to the treatment plan may be made in the operating room before and during PDT to optimize light delivery.

Algorithms↗

PubMed2004

Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy.

It is desirable to quantify the distribution of the light fluence rate, the optical properties, the drug concentration, and the tissue oxygenation for photodynamic therapy (PDT) of prostate cancer. We have developed an integrated system to determine these quantities before and after PDT treatment using motorized probes. The optical properties (absorption (micro(a)), transport scattering (micro(s'), and effective attenuation (micro(eff)) coefficients) of cancerous human prostate were measured in-vivo using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu) mediated PDT at different locations along each catheter. The light fluence rate distribution was also measured along the catheters during PDT. Diffuse absorption spectroscopy measurement using a white light source allows extrapolation of the distribution of oxygen saturation StO2, total blood volume ([Hb]t), and MLu concentration. The distribution of drug concentration was also studied using fluorescence from a single optical fiber, and was found to be in good agreement with the values determined by absorption spectroscopy. This study shows significant inter- and intra-prostatic variations in the tissue optical properties and MLu drug distribution, suggesting that a real-time dosimetry measurement and feedback system for monitoring these values during treatment should be considered in future PDT studies.

Dose-Response Relationship, Drug↗

PubMed2004

Thermal and temporal response of ionization chambers in radiation dosimetry.

The temporal and thermal response of various commonly used ion chambers (NEL, Exradin, PTW) with different wall and electrode materials is studied in a water phantom. Measurements were taken in heating water bath having an automatic temperature control mechanism. All chambers were submersed at 3 cm depth in water phantom and connected to separate electrometers for simultaneous readings for a given dose from a 6 MV beam. The temporal response was studied at approximately +/- 10 degrees C from room temperature, i.e., 10 degrees C and 30 degrees C. Temporal results show that all chambers reach quick equilibrium response within < 2 minutes of submersion in water. The steady-state thermal response was dependent upon the water temperature and wall and electrode compositions. The temperature and pressure corrected response of the NEL chamber was least affected by the changes in water temperature, where as the Exradin chamber has positive and PTW has negative slope with water temperature. The response varied within +/-1.5% between 10 degrees C-50 degrees C temperature and is mainly dependent on volume changes rather than the humidity. A correction factor based on thermal coefficients is derived for each chamber. It is concluded that ion chamber correction factors can be divided into first order; temperature and pressure connection, second order; volume correction for thermal expansion, and third order; humidity correction. To eliminate dosimetric error, the temporal and thermal response should be known for a chamber or water phantom temperature should be maintained close to room temperature.

Calibration↗

PubMed2004

Dose rate and SDD dependence of commercially available diode detectors.

The dose-rate dependence of commercially available diode detectors was measured under both high instantaneous dose-rate (pulsed) and low dose rate (continuous, Co-60) radiation. The dose-rate dependence was measured in an acrylic miniphantom at a 5-cm depth in a 10 x 10 cm2 collimator setting, by varying source-to-detector distance (SDD) between at least 80 and 200 cm. The ratio of a normalized diode reading to a normalized ion chamber reading (both at SDD=100 cm) was used to determine diode sensitivity ratio for pulsed and continuous radiation at different SDD. The inverse of the diode sensitivity ratio is defined as the SDD correction factor (SDD CF). The diode sensitivity ratio increased with increasing instantaneous dose rate (or decreasing SDD). The ratio of diode sensitivity, normalized to 4000 cGy/s, varied between 0.988 (1490 cGy/s)-1.023 (38,900 cGy/s) for unirradiated n-type Isorad Gold, 0.981 (1460 cGy/s)-1.026 (39,060 cGy/s) for unirradiated QED Red (n type), 0.972 (1490 cGy/s)-1.068 (38,900 cGy/s) for preirradiated Isorad Red (n type), 0.985 (1490 cGy/s)-1.012 (38,990 cGy/s) for n-type Pt-doped Isorad-3 Gold, 0.995 (1450 cGy/s)-1.020 (21,870 cGy/s) for n-type Veridose Green, 0.978 (1450 cGy/s)-1.066 (21,870 cGy/s) for preirradiated Isorad-p Red, 0.994 (1540 cGy/s)-1.028 (17,870 cGy/s) for p-type preirradiated QED, 0.998 (1450 cGy/s)-1.003 (21,870 cGy/s) for the p-type preirradiated Scanditronix EDP20(3G), and 0.998 (1490 cGy/s)-1.015 (38,880 cGy/s) for Scanditronix EDP10(3G) diodes. The p-type diodes do not always show less dose-rate dependence than the n-type diodes. Preirradiation does not always reduce diode dose-rate dependence. A comparison between the SDD dependence measured at the surface of a full scatter phantom and that in a miniphantom was made. Using a direct adjustment of radiation pulse height, we concluded that the SDD dependence of diode sensitivity can be explained by the instantaneous dose-rate dependence if sufficient buildup is provided to eliminate electron contamination. An energy independent empirical formula was proposed to fit the dose-rate dependence of diode sensitivity.

Equipment Failure Analysis↗

PubMed2004

Output ratio in air for MLC shaped irregular fields.

For accurate monitor unit calculation, it is important to calculate the output ratio in air, Sc, for an irregular field shaped by MLC. We have developed an algorithm to calculate Sc based on an empirical model [Med. Phys. 28, 925-937 (2001)] by projecting each leaf position to the isocenter plane. Thus it does not require the exact knowledge of the head geometry. Comparisons were made for three different types of MLC: those with MLC replacing the inner collimator jaws; those with MLC replacing the outer collimator jaws; and those with MLC as a tertiary attachment. When the MLC leaf positions are substantially different from the secondary collimators (or the rectangular field encompassing the irregular field), one observes an up to 5% difference in the value of head-scatter correction factor, HCF, defined as the ratio of output ratio in air between the MLC shaped irregular field and that of the rectangular field encompassing the irregular field. No collimator exchange effect was observed for rectangular fields shaped by MLC (e.g., 5x30 and 30x5 cm2 diagonal) when the secondary collimators are fixed, unlike that for the rectangular fields shaped by the inner and outer collimator jaws, where it can be 1-2%. For the same MLC shaped irregular field, the value of Sc increases from the Elekta, to the Siemens, to the Varian accelerators, with an up to 4% difference. The calculation agrees with measurement to within 1.2% for points both on and off the central-axis. The fitting parameters used in the algorithm are derived from measurements for square field sizes on the central-axis.

Algorithms↗

PubMed2003

Head scatter off-axis for megavoltage x rays.

Our objective in this study has been to investigate how head scatter varies with the off-axis position in a 6 MV x-ray beam. We define the head-scatter off-axis ratio, HOA, as the ratio of the kerma due to head-scatter photons at the off-axis position x to the kerma from direct primary photons on the central axis. "Direct primary" are those photons that come from the source without interactions in the intervening structures. We determined HOA from measurements with an ionization chamber in a miniphantom. Head-scatter and direct primary photons contribute to a measurement of the ionization per mu Q(x) at the off-axis position x in the open field cx x cy. The ionization per mu QP(x), measured in the same position but with the field collimated to the smallest possible opening (cx x 3 cm), is intended to include only direct primary photons. Head-scatter photons cannot be completely eliminated, and the errors due to remaining head scatter and radiation back-scattered by the movable collimators into the monitor were estimated. For normalization of the final results, ionization due to direct primary photons was also measured on the central axis, QP(0). HOA was derived from these three measurements as HOA(cx,cy,x)=(Q(cx,cy,x) - QP(cx,cy,x))/QP(cx,cy,0). On the central axis (x=y=0), HOA represents the "scatter-to-primary ratio" between head scatter and the direct primary dose. Monte Carlo simulations were made to help with the interpretation and evaluation of the results. HOA could be fitted to a Gaussian model with two components corresponding to sources of widths 1.8 and 14 cm, projected on a plane 5 cm below the x-ray source. The narrow Gaussian component is interpreted as the source of photons scattered in the flattening filter and the primary collimator. The broad component is attributed to photons scattered in the secondary (variable) collimators. Conventional head-scatter models (e.g., a single Gaussian source model) do not fit the measured HOA data for large collimator settings (c>20 cm) or outside beam collimation. The full width at half-maximum (FWHM) of HOA(x) across the field increased with the field width (cx) in the direction of the measurements in a manner consistent with the field of view of the two sources. It was not sensitive to the field measure in the orthogonal direction (cy). Head scatter outside the field also increased with field size, reflecting an increased contribution of photons scattered at large angles. It exceeds the leakage through the collimator 2 cm outside the edge for square fields c>10 cm. Monte Carlo calculations showed considerably less head scatter outside the field than measurements.

Air↗

PubMed2003

Modeling the instantaneous dose rate dependence of radiation diode detectors.

The sensitivity S of Si diodes generally increases with an increase in the instantaneous dose rate r of the radiation beam from clinical linear accelerators. A theoretical model is established to understand the physical origin of this dependence. During a radiation exposure, a portion of the excess minority carriers (electrons or holes) generated in the diode is captured by the R-G (recombination-generation) centers and is recombined with the majority carriers. The captured portion depends on the excess minority-carrier concentration delta p (proportional to r), the R-G center concentration N(t), and the minority-carrier capture cross-sections (sigma(n) for electrons and sigma(p) for holes) by the R-G center. When r increases, the R-G center concentration may not be sufficient to keep the recombination portion constant, which leads to an increase in diode sensitivity because a larger fraction of the charge will be collected. Larger majority-carrier concentration increases the recombination probability of the excess minority carriers and thus decreases the r dependence. The ratio of minority-carrier capture cross-sections, sigma(p)/sigma(n), influences the magnitude of the r dependence and also differentiates the r dependence between n-type and p-type diodes. A number of different circumstances can occur in diodes. When sigma(p) > sigma(n), such as for the dominant R-G center generated by electron radiation, the sensitivity is more dependent on r in an n-type diode than in a p-type diode if all the other device parameters are the same. When sigma(p) < sigma(n), the sensitivity is then more dependent on r in a p-type diode than in an n-type diode. The condition of sigma(p) < sigma(n) can occur when R-G centers with this property are generated by the foundry die process. A diode could have very small r dependence due to large R-G center concentration, generated by heavy platinum doping or radiation accumulated dose. Experimental data are compared with theory.

Computer Simulation↗

PubMed2003

In vivo optical properties of normal canine prostate at 732 nm using motexafin lutetium-mediated photodynamic therapy.

The optical properties (absorption [mu(a)], transport scattering [mu('s)] and effective attenuation [mu(eff)] coefficients) of normal canine prostate were measured in vivo using interstitial isotropic detectors. Measurements were made at 732 nm before, during and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). They were derived by applying the diffusion theory to the in vivo peak fluence rates measured at several distances (3, 6, 9, 12 and 15 mm) from the central axis of a 2.5 cm cylindrical diffusing fiber (CDF). Mu(a) and mu('s) varied between 0.03-0.58 and 1.0-20 cm(-1), respectively. Mu(a) was proportional to the concentration of MLu.Mu(eff) varied between 0.33 and 4.9 cm(-1) (mean 1.3 +/- 1.1 cm(-1)), corresponding to an optical penetration depth (8 = 1/(mu(eff)) of 0.5-3 cm (mean 1.3 +/- 0.8 cm). The mean light fluence rate at 0.5 cm from the CDF was 126 +/- 48 mW/cm2 (N = 22) when the total power from the fiber was 375 mW (150 mW/cm). This study showed significant inter- and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be advocated for future PDT studies. However, no significant changes were observed before, during and after PDT within a single treatment site.

Animals↗

PubMed2002

In vivo reflectance measurement of optical properties, blood oxygenation and motexafin lutetium uptake in canine large bowels, kidneys and prostates.

Motexafin lutetium (MLu) is a second-generation photosensitizer for photodynamic therapy (PDT) of cancer. We have developed and applied a diffuse optical reflectance spectrometer for in vivo measurement of MLu uptake, optical properties, haemoglobin concentration and haemoglobin oxygen saturation in normal canine large bowels, kidneys and prostates. The probe consists of a broadband fibre-optic-coupled light source and detector fibres placed at various distances from the source fibre to collect reflected light. An analysis based on the diffusion approximation of the photon transport equation was used to recover tissue optical properties from the reflectance measurements. The instrumentation and analysis methods were validated using measurements from homogeneous, highly scattering phantoms with known MLu concentrations. The same techniques were then used to estimate chromophore concentrations of normal canine large bowels, kidneys and prostates. We estimated (mean (standard deviation)) total haemoglobin concentrations of 119 (25), 340 (92) and 51 (11) microM in the large bowels, kidneys and prostates of four dogs, respectively; tissue blood oxygen saturations in these same organs were 75 (15), 76 (21) and 74 (16) per cent, respectively. Tissue MLu concentrations (mg l(-1)) were estimated from data taken 3.5 h after injection of a 2 mg kg(-1) injected dose; data from three dogs gave concentrations of 2.4 (0.4) in large bowels, 6.8 (1.3) in kidneys and 2.2 (1.1) in prostates. The reduced scattering coefficients, mu's, estimated for large bowels, kidneys and prostates at 730 nm were, respectively: 10.1 (1.3), 19.6 (4.0) and 12.7 (0.6) cm(-1). We observed significant variability in MLu uptake, tissue scattering and haemoglobin concentration between organs and even between the same organ in different dogs. This class of in situ optical property measurement may be desirable to individualize PDT drug and light delivery.

Algorithms↗

PubMed2002

In vivo light dosimetry for motexafin lutetium-mediated PDT of recurrent breast cancer.

BACKGROUND AND OBJECTIVES: To measure the fluence at tissue surface for patients in our Phase II clinical trial of motexafin lutetium (MLu)-mediated chest wall photodynamic therapy for recurrent breast carcinoma and to compare it to the calculated irradiance. STUDY DESIGN/MATERIALS AND METHODS: The spatial and time dependence of light fluence (rate) was monitored in vivo on the chest wall surface using isotropic detectors in five patients. Patients were given MLu either 4 mg/kg with light at 18 hours or 5 mg/kg with light at 24 hours using an irradiance of 150 J/cm(2) at 730 nm, with an incident fluence rate of 75 mW/cm(2). The ratio of fluence rate to the incident fluence rate was determined at the center of the treatment field. This ratio was used to estimate the effective attenuation coefficient, mu (eff). RESULTS: The mean and standard deviation of the ratio for all patients was 1.6 +/- 0.2. The corresponding range of mu (eff) was between 0.87 and 2.1 cm(-1), assuming reduced scattering coefficient, mu (s) = 4 cm(-1). CONCLUSIONS: A conversion factor was determined to convert the irradiance to fluence rate on the tissue surface. However, the fluence (or the ratio) on patient surface varied by 70% due to the heterogeneity of optical properties. This supports the use of real-time in vivo dosimetry during photodynamic therapy.

Adult↗

PubMed2002

Temperature dependence of commercially available diode detectors.

Temperature dependence of commercially available n- and p-type diodes were studied experimentally under both high instantaneous dose rate (pulsed) and low dose rate (continuous) radiation. The sensitivity versus temperature was measured at SSD = 80 or 100 cm, 10 x 10 cm2, and 5 cm depth in a 30 x 30 x 30 cm3 water phantom between 10 degrees C and 35 degrees C. The response was linear for all the diode detectors. The temperature coefficient (or sensitivity variation with temperature, svwt) was dose rate independent for preirradiated diodes. They were (0.30 +/- 0.01)%/degrees C, (0.36 +/- 0.03)%/degrees C, and (0.29 +/- 0.08)%/degrees C for QED p-type, EDP p-type, and Isorad n-type diodes, respectively. The temperature coefficient for unirradiated n-type diodes was different under low dose rate [(0.16 to 0.45)%/degrees C, continuous, cobalt] and high instantaneous dose rate [(0.07 +/- 0.02)%/degrees C, pulsed radiation]. Moreover, the temperature coefficient varies among individual diodes. Similarly, the temperature coefficient for a special unirradiated QED p-type diode was different under low dose rate (0.34%/degrees C, cobalt) and high instantaneous dose rate [(0.26 +/- 0.01)%/degrees C, pulsed radiation]. Sufficient preirradiation can eliminate dose rate dependence of the temperature coefficient. On the contrary, preirradiation cannot eliminate dose rate dependence of the diode sensitivity itself.

Phantoms, Imaging↗

PubMedDate not supplied

Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy.

We evaluate Photofrin-mediated photodynamic therapy (PDT) in a phase 2 clinical trial as an adjuvant to surgery to treat peritoneal carcinomatosis. We extract tissue optical [reduced scattering (mu(s)'), absorption (mu(a)), and attenuation coefficients (mu(eff))] and physiological [blood oxygen saturation (%S(t)O2), total hemoglobin concentration (THC), and photosensitizer concentration (c(Photofrin))] properties in 12 patients using a diffuse reflectance instrument and algorithms based on the diffusion equation. Before PDT, in normal intraperitoneal tissues %S(t)O2 and THC ranged between 32 to 100% and 19 to 263 microM, respectively; corresponding data from tumor tissues ranged between 11 to 44% and 61 to 224 microM. Tumor %S(t)O2 is significantly lower than oxygenation of normal intraperitoneal tissues in the same patients. The mean (+/-standard error of mean) penetration depth (delta) in millimeters at 630 nm is 4.8(+/-0.6) for small bowel, 5.2 (+/-0.67) for large bowel, 3.39(+/-0.29) for peritoneum, 5.19(+/-1.4) for skin, 1.0(+/-0.1) for liver, and 3.02(+/-0.66) for tumor. c(Photofrin) in micromolars is 4.9(+/-2.3) for small bowel, 4.8(+/-2.3) for large bowel, 3.0 (+/-1.0) for peritoneum, 2.5(+/-0.9) for skin, and 7.4(+/-2.8) for tumor. In all tissues examined, mean c(Photofrin) tends to decrease after PDT, perhaps due to photobleaching. These results provide benchmark in-vivo tissue optical property data, and demonstrate the feasibility of in-situ measurements during clinical PDT treatments.

Algorithms↗

PubMedDate not supplied

Optical properties of human prostate at 732 nm measured in mediated photodynamic therapy.

Characterization of the tissue light penetration in prostate photodynamic therapy (PDT) is important to plan the arrangement and weighting of light sources so that sufficient light fluence is delivered to the treatment volume. The optical properties (absorption [mu(a)], transport scattering [mu(s)'] and effective attenuation [mu(eff)] coefficients) of 13 patients with locally recurrent prostate cancer were measured in situ using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu)-mediated PDT in four quadrants. Optical properties were derived by applying the diffusion theory to the fluence rates measured at several distances (0.5-5 cm) from a point source. mu(a) and mu(s)' varied between 0.07 and 1.62 cm(-1) (mean 0.37 +/- 0.24 cm(-1)) and 1.1 and 44 cm(-1) (mean 14 +/- 11 cm(-1)), respectively. mu(a) was proportional to the concentration of MLu measured by an ex vivo fluorescence assay. We have observed, on average, a reduction of the MLu concentration after PDT, presumably due to the PDT consumption of MLu. mu(eff) varied between 0.91 and 6.7 cm(-1) (mean 2.9 +/- 0.7 cm(-1)), corresponding to an optical penetration depth (delta = 1/micro(eff)) of 0.1-1.1 cm (mean 0.4 +/- 0.1 cm). The mean penetration depth at 732 nm in human prostate is at least two times smaller than that found in normal canine prostates, which can be explained by a four times increase of the mean value of mu(s)' in human prostates. The mean light fluence rate per unit source strength at 0.5 cm from a point source was 1.5 +/- 1.1 cm(-2), excluding situations when bleeding occurs. The total number of measurements was N = 121 for all mean quantities listed above. This study showed significant inter- and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be considered for future PDT studies.

Humans↗

PubMedDate not supplied

Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy.

The in vivo fluorescence emission from human prostates was measured before and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). A single side-firing optical fiber was used for both the delivery of 465 nm light-emitting diode excitation light and the collection of emitted fluorescence. It was placed interstitially within the prostate via a closed transparent plastic catheter. Fitting of the collected fluorescence emission spectra using the known fluorescence spectrum of 1 mg/kg MLu in an intralipid phantom yields a quantitative measure of the local MLu concentration. We found that an additional correction factor is needed to account for the reduction of the MLu fluorescence intensity measured in vivo due to strong optical absorption in the prostate. We have adopted an empirical correction formula given by C = (3.1 cm(-1)/micro's) exp (microeff x 0.97 cm), which ranges from approximately 3 to 16, with a mean of 9.3 +/-4.8. Using a computer-controlled step motor to move the probe incrementally along parallel tracks within the prostate we can determine one-dimensional profiles of the MLu concentration. The absolute MLu concentration and the shape of its distribution are confirmed by ex vivo assay and by diffuse absorption measurements, respectively. We find significant heterogeneity in photosensitizer concentration within and among five patients. These variations occur over large enough spatial scales compared with the sampling volume of the fluorescence emission that mapping the distribution in three dimensions is possible.

Humans↗

PubMedDate not supplied

Real-time in situ monitoring of human prostate photodynamic therapy with diffuse light.

Photodynamic therapy (PDT) requires oxygen to cause cellular and vascular tumor damage. Tissue oxygen concentration, in turn, is influenced by blood flow and blood oxygenation. Real-time clinical measurement of these hemodynamic quantities, however, is rare. This paper reports the development and application of a probe, combining diffuse reflectance spectroscopy (DRS) for measurement of tumor blood oxygenation and diffuse correlation spectroscopy (DCS) for measurement of tumor blood flow. The instrument was adapted for clinical use during interstitial prostate PDT. Three patients with locally recurrent prostate cancer received 2 mg/ kg motexafin lutetium (MLu) 3 h before illumination and a total light dose of 100 J/cm(2) at 150 mW/cm. Prostrate blood oxygen saturation (StO2) decreased only slightly (approximately 3%) after treatment. On the other hand, prostate blood flow and total hemoglobin concentration over the course of PDT decreased by 50% and 15%, respectively, suggesting MLu-mediated PDT has an anti-vascular effect. While it is certainly impossible to draw definite conclusions from measurements of only three patients, the observed differences in tumor blood flow and blood oxygenation responses during PDT can, in principle, be used to choose among tissue oxygen consumption models and therefore emphasize the potential clinical value for simultaneous monitoring of both parameters.

Dose-Response Relationship, Radiation↗