Biomedical subjects

J P Marijnissen

Publications and source records attributed to J P Marijnissen.

At least 19 recordsLinked to original sources

PubMed2000

Three-dimensional intravascular ultrasound assessment of noninjured edges of beta-irradiated coronary segments.

BACKGROUND: The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation. METHODS AND RESULTS: Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. CONCLUSIONS: The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

Angioplasty, Balloon↗

PubMed2000

Residual plaque burden, delivered dose, and tissue composition predict 6-month outcome after balloon angioplasty and beta-radiation therapy.

BACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA. METHODS AND RESULTS: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque. CONCLUSIONS: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA.

Angioplasty, Balloon, Coronary↗

PubMed2000

Relationship between tensile stress and plaque growth after balloon angioplasty treated with and without intracoronary beta-brachytherapy.

AIMS: We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy. METHODS AND RESULTS: Thirty-one consecutive patients successfully treated with balloon angioplasty were analysed qualitatively and quantitatively by means of an ECG-gated three-dimensional intravascular ultrasound post-procedure and at follow-up. Eighteen patients were irradiated with catheter-based beta-radiation ((90)Sr/(90)Y source) and 13 were not (control). Studied segments were divided into 2 mm subsegments. Thus 184 irradiated and 111 non-irradiated subsegments were included. Tensile stress was calculated according to Laplace's law. The radiation dose was calculated by means of dose-volume histograms. Plaque growth was positively correlated to tensile stress in both the radiation and control groups (r=0.374, P=0.0001 and r=0.305, P=0.001). Low-dose subsegments (<6 Gy) had a significant correlation (r=0.410, P=0.0001) whereas no correlation was observed in the effective-dose subsegments (> or = 6 Gy). Multivariate analysis identified tensile stress as the only independent predictor of plaque increase in non-irradiated subsegments, whereas actual dose and plaque morphology were stronger predictors in irradiated subsegments. CONCLUSION: The results of this study suggest that plaque growth is related to tensile stress after balloon angioplasty. Intracoronary brachytherapy may alter the biophysical process on plaque growth when the prescribed dose is effectively delivered.

Aged↗

PubMed1999

Preserved endothelium-dependent vasodilation in coronary segments previously treated with balloon angioplasty and intracoronary irradiation.

BACKGROUND: Abnormal endothelium-dependent coronary vasomotion has been reported after balloon angioplasty (BA), as well as after intracoronary radiation. However, the long-term effect on coronary vasomotion is not known. The aim of this study was to evaluate the long-term vasomotion of coronary segments treated with BA and brachytherapy. METHODS AND RESULTS: Patients with single de novo lesions treated either with BA followed by intracoronary beta-irradiation (according to the Beta Energy Restenosis Trial-1.5) or with BA alone were eligible. Of these groups, those patients in stable condition who returned for 6-month angiographic follow-up formed the study population (n=19, irradiated group and n=11, control group). Endothelium-dependent coronary vasomotion was assessed by selective infusion of serial doses of acetylcholine (ACh) proximally to the treated area. Mean luminal diameter was calculated by quantitative coronary angiography both in the treated area and in distal segments. Endothelial dysfunction was defined as a vasoconstriction after the maximal dose of ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated normal endothelial function. In contrast, 10 distal nonirradiated segments (53%) and 5 control segments (45%) demonstrated endothelium-dependent vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage of change in mean luminal diameter after ACh was significantly higher in irradiated segments (P=0.01). CONCLUSIONS: Endothelium-dependent vasomotion of coronary segments treated with BA followed by beta-radiation is restored in the majority of stable patients at 6-month follow-up. This functional response appeared to be better than those documented both in the distal segments and in segments treated with BA alone.

Acetylcholine↗

PubMed1999

Short- and long-term normal tissue damage with photodynamic therapy in pig trachea: a fluence-response pilot study comparing Photofrin and mTHPC.

The damage to normal pig bronchial mucosa caused by photodynamic therapy (PDT) using mTHPC and Photofrin as photosensitizers was evaluated. An endobronchial applicator was used to deliver the light with a linear diffuser and to measure the light fluence in situ. The applied fluences were varied, based on existing clinical protocols. A fluence finding experiment with short-term (1-2 days) response as an end point showed considerable damage to the mucosa with the use of Photofrin (fluences 50-275 J cm(-2), drug dose 2 mg kg(-1)) with oedema and blood vessel damage as most important features. In the short-term mTHPC experiment the damage found was slight (fluences 12.5-50 J cm(-2), drug dose 0.15 mg kg(-1)). For both sensitizers, atrophy and acute inflammation of the epithelium and the submucosal glands was observed. The damage was confined to the mucosa and submucosa leaving the cartilage intact. A long-term response experiment showed that fluences of 50 J cm(-2) for mTHPC and 65 J cm(-2) for Photofrin-treated animals caused damage that recovered within 14 days, with sporadic slight fibrosis and occasional inflammation of the submucosal glands. Limited data on the pharmacokinetics of mTHPC show that drug levels in the trachea are similar at 6 and 20 days post injection, indicating a broad time window for treatment. The importance of in situ light dosimetry was stressed by the inter-animal variations in fluence rate for comparable illumination conditions.

Animals↗

PubMed1998

Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound.

Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.

Brachytherapy↗

PubMed1997

Improvements in the design of linear diffusers for photodynamic therapy.

The angular radiance distribution of several linear diffusers used for photodynamic therapy (PDT) was measured. The forward scattering found previously was not observed for these designs. The improved isotropy leads to a better agreement between intended treatment site and actual maximum of the fluence rate profile when the linear diffuser is used in a hollow, cylindrical organ.

Diffusion↗

PubMed1996

Use of sheet color filters for video-endoscopic observation during intraluminal photodynamic therapy.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is currently evaluated in clinical studies for the treatment of bronchial and oesophageal tumors. STUDY DESIGN/MATERIALS AND METHODS: Usually, a cylindrical diffuser is entered into the lumen via a flexible endoscope. Subsequently, the diffuser is positioned at the tumor location under direct- or video-endoscopic vision and manually kept in position by the clinician during the treatment. However, video endoscopes are saturated (overexposure) due to the intense light from the diffuser tip and scattered light from the tissue. This hinders continuous monitoring of the diffuser position. RESULTS: A simple color filter sheet, suitable for use with endoscopes with removable CCD-video head, appeared to be very effective in improving video endoscopic monitoring during treatment. CONCLUSION: The standard fiberoptic endoscopes with the accessory CCD video head are more suitable for PDT treatment monitoring than modern endoscopes with the integrated CCD camera.

Bronchial Neoplasms↗

PubMed1996

Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma.

The goal of this study was to investigate the efficacy of photodynamic therapy (PDT) of a single tumour growing intraperitoneally. For this purpose the CC531 colon carcinoma, implanted in an intraperitoneal fat pad of Wag/RijA rats, was treated with intraperitoneal photodynamic therapy (IPPDT) using Photofrin as the photosensitiser. Two illumination techniques have been compared. An invasive illumination technique using Perspex blocks to illuminate 30 cm2 of the lower abdomen gave a significant delay in tumour growth with 25 J cm-2 applied 1 day after Photofrin. A minimally invasive illumination technique using a balloon catheter to illuminate 14 cm2 resulted in an equivalent growth delay with 75 J cm-2. The route of administration of the photosensitiser did not influence regrowth times of the tumour. Mitomycin C (MMC), a bioreductive agent, was used to exploit the known PDT-induced hypoxia. The combination of IPPDT with MMC resulted in an increased tumoricidal effect. In conclusion, IPPDT led to a significant growth delay for a single tumour implanted intraperitoneally and repetition of the PDT treatment was possible using a minimally invasive illumination technique. Repeated treatments resulted in increased tumour response.

Adenocarcinoma↗

PubMed1996

Light distribution by linear diffusing sources for photodynamic therapy.

The distribution of the light emitted by linear light diffusers commonly employed in photodynamic therapy (PDT) has been investigated. A device is presented which measures the angular distribution of the exiting light at each point of the diffuser. With these data the fluence rate in air or in a cavity at some distance from the diffuser can be predicted. The results show that the light is scattered from the diffuser predominantly in the forward direction. Experiments and calculations show that the fluence rate in air and in a cavity of scattering tissue at some distance from the diffuser has a maximum near the tip of the diffuser, instead of near the middle. However, the fluence rate resulting from an interstitial diffuser in a purely scattering tissue phantom shows a maximum in the bisecting plane of the diffuser as would be predicted when the diffuser emitted light isotropically. The scattering nature of the tissue is expected to cancel the anisotropy of the diffuser.

Animals↗

PubMed1996

Calibration of isotropic light dosimetry probes based on scattering bulbs in clear media.

Miniature light detectors with isotropic response (isotropic light probes) permit quantitative measurement of light energy fluence rates in turbid media such as biological tissues. These isotropic probes are, for example, applied in photodynamic therapy to correlate light fluence in tissue with (tumour) tissue response, in vitro and in vivo. After description of its construction, two methods of calibration of an isotropic probe in air are discussed, in collimated and in diffuse light. The probe was first calibrated in air in collimated light, after which its response to diffuse light was checked in a flat and in a spherical geometry. Subsequently, the probe's response to collimated light in clear media, for example, water or glycerine which have refractive indices larger than that of air, has been established experimentally. The diffusion approximation to the transport equation in a simple spherical geometry has been used to calculate the probe's response as a function of the refractive index of clear media. The extent of agreement between theory and experiment indicates that the physical mechanisms are understood and indirectly validates the theoretical models.

Humans↗

PubMed1996

Influence of fractionation and fluence rate in photodynamic therapy with Photofrin or mTHPC.

Various schedules of fractionated photodynamic therapy (PDT), delivered at two different light fluence rates, were investigated in the RIF1 tumor model in an attempt to minimize the development of hypoxia during PDT and thereby improve tumor response relative to single treatments. The photosensitizers Photofrin and meta-tetrahydroxyphenylchlorin (mTHPC) were used in combination with either interstitial or superficial illumination. For both methods of illumination, equal volumetric light doses gave similar tumor responses, as measured by tumor regrowth times and number of cures. Fractionation of superficial illumination did not generally improve tumor response compared with a single illumination with the same total light dose. The only fractionated schedules which demonstrated a trend for increased cure were six fractions of superficial illumination given with short (1 h) dark periods between illuminations. Using both photosensitizers, an increase in tumor regrowth time occurred when tumors were illuminated interstitially with continuous light at a linear diffuser output of 50 mW compared with 100 mW per cm diffuser length. Discontinuous illumination with alternating light and dark periods of 30 s improved the tumor response further for mTHPC-mediated PDT at a fluence rate of 100 mW cm(-1). No improvement in response was seen by discontinuous interstitial illumination after Photofrin-mediated PDT. These results demonstrate that lower fluence rates and/or fractionating the light dose delivered can improve the response of the RIF1 tumor to PDT but that the choice of dark intervals between fractions is critical.

Animals↗

PubMed1995

Ex vivo light dosimetry and Monte Carlo simulations for endobronchial photodynamic therapy.

The light distribution during photodynamic therapy of the bronchial tree has been estimated by measuring the fluence rate in ex vivo experiments on dissected pig bronchi. The trachea was illuminated (630 nm) with a cylindrical diffuser and the fluence rate was measured with a fibre optic isotropic probe. The experiment with the diffuser on the central axis was also simulated with Monte Carlo techniques using the optical properties that were determined with a double-integrating-sphere set-up. The results from ex vivo experiments and the Monte Carlo simulations were found to agree within the error of measurement (15%), indicating that the Monte Carlo technique can be used to estimate the light distribution for varying geometries and optical properties. The results showed that the light fluence rate in the mucosa of the tracheal tract may increase by a factor of six compared to the fluence rate in air (in the absence of tissue). This is due to the scattering properties of the tissue and the multiple reflections within the cavity. Further ex vivo experiments showed that the positioning of the diffuser is critical for the fluence rate in the lesion to be treated. When the position of the diffuser was changed from the central axis to near the lesion, the fluence rate in the mucosa increased significantly by several orders of magnitude as compared to the initial (central) illumination. The inter- and intraspecimen variations in this increase were large (+/- 35%) because of variations in optical and geometrical properties and light source positioning, respectively. These variations might cause under- or overdosage resulting in either insufficient tumour necrosis or excessive normal tissue damage.

Animals↗

PubMed1994

Intraperitoneal photodynamic therapy in the rat: comparison of toxicity profiles for photofrin and MTHPC.

Toxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652-nm wave-length, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J.cm-2 delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J.cm-2 at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC-mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J.cm-2 at 24 hr after Photofrin or 8-12 J.cm-2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole-abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers caused similar toxicity profiles depending on drug dose, light fluence and time interval.

Animals↗

PubMed1993

In situ light dosimetry during whole bladder wall photodynamic therapy: clinical results and experimental verification.

Photodynamic therapy (PDT) using Photofrin IIR (PII) as a photosensitizer is currently being evaluated as a new treatment modality for superficial bladder cancer. An optimum therapeutic ratio requires uniform illumination of the whole bladder wall and accurate light dosimetry. The first clinical light dosimetry results (16 patients) are reported, obtained using a system which allows in situ measurement and control of the light fluence at the bladder wall. The true light fluence at the bladder wall (i.e. non-scattered incident light plus scattered light) appeared to be on the average a factor beta = 4.8 +/- 1.2 (mean +/- SD) larger than the non-scattered incident light fluence. The latter is often, but incorrectly, used in reporting light fluence. The factor beta varied between patients with extremes of 2.5 and 7.1. Because such large variations were unexpected, but may have significant clinical consequences, experiments in plastic bladder models were performed to study separately the various factors (e.g. bladder shape, air bubble) affecting the dosimetry in clinical treatments. The results imply that the clinical variations are most likely to be the result of variations in optical properties of the bladder wall mucosa, probably due to the disease and prior treatments. If light dosage is based on non-scattered light only (without in situ light dosimetry, according to a current clinical protocol) the present results indicate variations in the true (total) light fluence between patients by a factor of at least 2. At the least this may cause unnecessary discomfort to a number of patients.

Female↗

PubMed1993

Pilot study on light dosimetry for endobronchial photodynamic therapy.

Endobronchial photodynamic therapy (EB-PDT) using photofrin as the photosensitizer is currently being evaluated as a new treatment modality for inoperable endobronchial tumors. One of the current problems with EB-PDT is the lack of adequate light dosimetry, which hampers proper interpretation of treatment results. In this study exploratory light dosimetry experiments were performed in plastic bronchus models using either a microlens-tipped fiber (suitable for illumination of small superficial tumors) or a cylindrical diffuser fiber (suitable for intraluminal illumination or interstitial illumination of partially obstructing tumors). It is shown that the light fluence prescriptions of current clinical protocols yield a different fluence in tissue for each illumination modality. Depending on the actual placement of the cylindrical diffuser within the lumen, the light fluence at 5 mm depth in the homogeneous tissue model may vary by a factor of 3. The results were confirmed by in vivo experiments in the trachea of a pig. There is a possibility of enhanced tissue response by accidental hyperthermia induced during EB-PDT. The temperature rise was therefore estimated in vivo using a rat tumor model to mimic clinical EB-PDT. Temperature rises of at least 5 degrees C and 10 degrees C can be expected for intraluminal and intratumoral illumination, respectively, at 3.5 +/- 1 mm depth in tissue and 400 mW/cm diffuser output. Light fluence and its distribution in the bronchus strongly depend on the geometry and the optical properties of the tissue as well as on the technique of illumination. As a result of inadequate dosimetry, significant variations in treatment response between patients may be expected.

Animals↗

PubMed1992

Tumor and normal tissue response to interstitial photodynamic therapy of the rat R-1 rhabdomyosarcoma.

Interstitial photodynamic therapy (IPDT) using Photofrin II (PII) as photosensitizer has been studied in the rat rhabdomyosarcoma R-1, growing on the thigh or flank of WAG-Rij rats. A light dose-response relationship has been established, for 10 mg PII/kg i.v. and irradiation 24 hr later, with local tumor control as the end point for single IPDT treatments using four cylindrical diffusors simultaneously. A light energy fluence of 150-200 Joule/cm2 (wavelength 625 nm), measured in vivo at the tumor periphery, was required for tumor control. Comparison of tumor response at 5 and 2.5 mg PII/kg with the complete dose response relationship at 10 mg PII/kg suggests drug-light dose reciprocity and indicates that in our tumor model treatment failures are not likely to be caused by variations in (tumor) tissue photosensitizer level, but rather by insufficient light dose or inadequate light dose distribution. Increasing the interval between PII administration and irradiation from 24 hr to 48 hr had no great effect on tumor response to IPDT in this study. Inspection of the original tumor site 100 days after tumor control revealed obvious loss of thigh muscle tissue. Also, recurrent tumors showed a reduced growth rate. Therefore, the relationship between tumor (re)growth and PDT-induced normal tissue damage was studied and the existence of a tumor bed effect was confirmed. The present study indicates that tumor control after a single IPDT treatment is feasible, but that PDT induced damage to a margin of the adjacent normal tissue is probably required.

Animals↗

PubMed1992

Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder.

We report on the preliminary results of 12 patients with multifocal carcinoma in situ of the bladder treated with whole bladder wall photodynamic therapy. The total light dose (scattered plus nonscattered light) measured in situ was 100 joules per cm.2 in the first 6 patients (group 1) and 75 joules per cm.2 in the remaining 6 (group 2). These light doses correspond on the average to 27 joules per cm.2 and 15.5 joules per cm.2 nonscattered light as reported by other investigators. Followup ranged from 6 to 22 months (average 11.5). In group 1, 2 tumors recurred after 6 and 9 months, respectively, and 2 other patients had a permanently shrunken bladder without evidence of disease. In group 2, 1 tumor recurred 5 months after photodynamic therapy. In this group the bladder capacity increased on the average to 135% of the pretreatment value 3 months after photodynamic therapy. All recurrences were in patients with a history of invasive bladder cancer (stages T1 and T2). These preliminary results demonstrate the importance of in situ scattered light dosimetry for minimizing local side effects of whole bladder photodynamic therapy.

Aged↗