Biomedical subjects

H Hirschberg

Publications and source records attributed to H Hirschberg.

At least 19 recordsLinked to original sources

PubMed2006

Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma.

OBJECTIVE: The feasibility of using ALA-mediated photodynamic therapy (PDT) tumor ablation as a minimally invasive treatment alternative for malignant brain tumors was evaluated in a rodent model. Treatment efficacy and side effects were evaluated with MRI, histopathology and survival rates. METHODS: BT (4)C orthotopic brain tumors were induced in BD-IX rats. At various time intervals following tumor induction the animals were given 5-aminolevulinic acid (ALA) and 4 hours later optical fibers were inserted directly into the tumor without mechanical debulking or cranial decompression. A 3-day course of steroid treatment was initiated immediately prior to PDT. RESULTS: All untreated animals inevitably died within one month after tumor implantation (28.5 +/- 2.5 days). Complete tumor eradication was achieved in only 1/17 rats, but a significant increase in survival was obtained in the group of animals receiving 125 mg/kg ALA and 26 Joules of light fluence. Histopathology revealed large areas of central tumor necrosis, although clusters of viable tumor cells were often found at the tumor periphery. Pronounced edema in the necrotic tumor center as well as in the surrounding brain, and along white matter tracts was evident in all the brains studied from PDT-treated animal. CONCLUSION: This study suggests that ALA-mediated PDT may become a promising alternative therapy for the minimally invasive treatment of brain tumors. A judicious choice of PDT regimens that minimizes inflammatory responses through the use multiple fractionated long-term treatment protocols would likely be required.

Aminolevulinic Acid↗

PubMed2005

Integrated neuronavigation system with intraoperative image updating.

OBJECTIVE: Recently, MRI has entered the field of image-guided surgery as a new intraoperative imaging modality. In spite of its obvious benefits, this type of iMRI scanner has some drawbacks that have limited its utilization. The goal of the work presented here was to overcome some of these disadvantages. METHODS: A system that allows intraoperative images to be acquired during surgery and have the ability to conduct surgery outside the constraints of the narrow gap of the open magnet was implemented. Ability to conduct tasks inside the scanner with real-time image guidance was also maintained. The system allowed navigation with neuronavigation tools both inside the gap of an open magnet and outside the magnet, utilizing two different optical camera-sets and a dynamic reference frame. Automatic patient registration was implemented. RESULTS: The average difference between tracking position measured outside and inside the magnet was 0.8 +/- 0.1 mm. CONCLUSION: In the work presented in this note we have introduced a dynamic reference frame to compensate for transport of the patient to a location outside the scanner employing a second camera set. The integrated system showed adequate accuracy.

Equipment Design↗

PubMed2005

Impact of intraoperative MRI on the surgical results for high-grade gliomas.

OBJECTIVE: The impact of intraoperative MRI (iMRI) on the surgical procedure, patient outcome and median survival for a series of patients harbouring high-grade gliomas forms the basis of this study. Their outcome has been compared to a matched cohort of patients operated in a conventional manner to determine if the use of intraoperative MRI can be shown to improve the results of surgery and prognosis for this type of patient. MATERIALS AND METHODS: 32 microsurgical open craniotomies, performed in the intraoperative iMRI scanner for grade IV supratentorial gliomas, with follow-up periods of more than 2 months, were analyzed for this study. A group of 32 primary high-grade glioma patients (no recurrent tumors) were matched for age, preoperative clinical grade, gender and histology and operated during a corresponding time interval in a conventional manner acted as controls. RESULTS: All 64 patients were examined and analyzed for the occurrence of postoperative increased neurological morbidity or death. No complications directly related to the intraoperative scanning procedures were observed and no intraoperative death occurred in either group. The average operating time in the intraoperative scanner was 5.1 hours and was significantly longer than in the conventional OR (3.4 hours). The mean overall survival time for the 32 patients in the study group was 14.5 months (95 % confidence interval 12.0 - 16.6) compared to 12.1 months (95 % confidence interval 10.2 - 14.1) for the matched control group. CONCLUSION: Although iMRI is an effective way of imaging residual tumor, this study could not demonstrate an increased efficacy of surgery utilizing this technique for patients harbouring grade IV gliomas compared to more conventional methods. No statistical significance was noted between the two groups (p = 0.14). The complication rate was within the range reported for other series, in both control as well as the study group.

Adult↗

PubMed2003

Image-guided stereotaxy in the interventional MRI.

BACKGROUND: Stereotactic procedures employing frame-based systems and utilizing pre-operative MR or CT have several shortcomings such as long procedure time, patient discomfort and transport, poor fail-safe capabilities and targeting inaccuracies due to brain shift. Conducting all procedural steps in an interventional MRI has the potential of alleviating some of these deficiencies. METHODS: A stereotactic system consisting of a skull-mounted mechanical positioning device and customized navigation software has been developed. The accuracy of this system was tested within an interventional MRI employing a skull phantom. RESULTS: The mean distance between the targets hit and the planned target coordinates was 0.70 mm +/- 0.3 mm with a maximum distance of 1.3 mm. INTERPRETATION: The results indicate that the proposed stereotactic system can be used for stereotactic procedures in the interventional MRI.

Brain Diseases↗

PubMed2001

Development of a novel indwelling balloon applicator for optimizing light delivery in photodynamic therapy.

BACKGROUND AND OBJECTIVE: A human glioma spheroid model is used to investigate the efficacy of different light delivery schemes in 5-aminolevulinic acid (ALA)--mediated photodynamic therapy (PDT). The results provide the rationale for the development of an indwelling balloon applicator for optimizing light delivery. STUDY DESIGN/MATERIALS AND METHODS: Human glioma spheroids were incubated in ALA (100 or 1000 microg /ml-1) for 4 hours and subjected to various light irradiation schemes. In one set of experiments, spheroid survival was monitored as a function of light fluence rate (5-200 mW cm-2). In all cases, spheroids were exposed to fluences of either 25 or 50 J cm-2. In a second study, the effects of repeated weekly PDT treatments, using sub-threshold fluences, were investigated. One group of spheroids was subjected to three treatments using fluences of 12, 12, and 25 J cm-2. Results were compared to spheroids receiving single treatments of either 12 or 25 J cm-2. A fluence rate of 25 mW cm-2 was used for all three groups of spheroids. In all cases, the effect of a given irradiation scheme was evaluated by monitoring spheroid growth. RESULTS: Low fluence rates produce greater cell kill than high fluence rates. The minimum effective fluence rate in human glioma spheroids is approximately 10 mW cm-2. Repeated weekly PDT treatments with sub-threshold fluences result in significant cell kill. In spheroids surviving the PDT treatments, growth is suppressed for the duration of the treatment period. CONCLUSION: The results of the in vitro studies support the development of an indwelling balloon applicator for the delivery of light doses in long term multi-fractionated PDT regimens.

Aminolevulinic Acid↗

PubMed2000

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).

Anti-Bacterial Agents↗

PubMed2000

Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid.

The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily convert ALA to protoporphyrin IX throughout the entire spheroid volume. The central finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rate at which the fluence is delivered. At low fluences (< or = 50 J cm-2), lower fluence rates are more effective. At a fluence of 50 J cm-2, near-total spheroid kill is observed at fluence rates of as low as 10 mW cm-2. The fluence rate effect is not as pronounced at higher fluences (> 50 J cm-2), where a favorable response is observed throughout the range of fluence rates investigated. The clinical implications of these findings are discussed.

Aminolevulinic Acid↗

PubMed1999

Neuronavigation in intraoperative MRI.

OBJECTIVE: We describe the development and implementation of an image-guided surgical system combining the best features of conventional frameless stereotactic systems and the recently developed superconductive vertically configured intraoperative magnetic resonance scanner. The incorporation of intraoperatively updated magnetic resonance imaging (MRI) data sets into the neuronavigation computer overcomes one of the main disadvantages of these systems, i.e., intraoperative brain shift. METHODS: The integrated system consists of a 0.5-T MRI scanner (Signa SP General Electric Medical Systems, Milwaukee, WI), a neuronavigation computer with associated software (OTS Radionics, Burlington, MA), and an emulation program linking the two. The scanner has a 60-cm-wide vertical gap where both imaging and surgery are conducted, in-bore infrared linear cameras and monitors for interactive surgical neuronavigation, and flexible surface coils specially designed for surgery. RESULTS: Phantom studies showed navigational accuracy to be better than that obtained using conventional preoperative images and surface markers for patient registration. Our initial 17 cases using this integrated system comprised 16 craniotomies and one biopsy, and demonstrated decreased operative duration, greater frequency of interactive image guidance utilization, and better assessment of the progress of surgery compared to the cases previously done in the intraoperative MRI. CONCLUSION: This initial study of the addition of frameless stereotactic systems to the basic intraoperative MRI concept has demonstrated its clinical usefulness. The use of the intraoperative MRI greatly reduces the basic weakness of neuronavigation inaccuracy due to target shift. The surgical procedure performed in the imaging volume of the MRI scanner eliminates the problems of patient or scanner transport during the procedure. Immobilization of the patient throughout the procedure eliminated the need for reregistration of the patient, by taking advantage of the fixed camera system in the bore of the MRI system.

Adult↗

PubMed1999

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.

Adult↗

PubMed1999

An indwelling brachytherapy balloon catheter: potential use as an intracranial light applicator for photodynamic therapy.

An indwelling balloon applicator developed for postoperative intracavity afterloading brachytherapy was evaluated for photodynamic therapy (PDT). Following tumor resection, the applicator is positioned in the center of the resultant cavity and the balloon is inflated with a scattering solution. The liquid-filled balloon stabilizes the resection cavity ensuring a constant and simple geometric shape during treatment. The catheter is brought out through the skin and adjusted so that 1-2 cm projects above the scalp surface. Measurements of light distribution in a phantom model surrounding the balloon catheter, show that it may be used to deliver sufficiently uniform light doses during PDT. The light distribution is uniform to within 5% when the balloon is filled with a scattering medium. Based on simple assumptions, it is shown that the applicator can be used to deliver a sufficient optical dose to brain tissue at a depth of 1 cm in less than 1 h. The applicator has already been used for brachytherapy in 72 patients with few complications. A new treatment protocol employing the combination of both fractionated intracavity brachytherapy and PDT is currently being planned.

Brachytherapy↗

PubMed1999

Intraoperative image-directed dye marking of tumor margins.

The incorporation of interactive image guidance during intracranial tumor surgery offers the possibilities of reduced operative trauma, shorter operation time, greater precision, and an increased understanding of complex anatomy and pathology. A basic weakness with these systems though is that they cannot account for movement of target points due to brain shift by draining of CSF or removal of pathology during the operative procedure. We have developed a stereotactic (frameless) guided injector probe for marking the tumor boundary with dye injection in conjunction with a neuronavigation system. The device consisted of a rigid blunt hollow probe (2 mm dia.) with 4 small side holes at the tip. The catheter is mounted in a holder equipped with 3 LEDs supplying guidance information for the neuronavigation system. A small manual aliquoting pump delivers a measured amount of dye in each track. Isotonic methylene blue was injected in 6 to 8 tracks around the periphery of the tumor as determined by the contract ring in MR scans. The dye was injected using image-directed guidance before resection of the tumor was started (often with the dura intact). Tumor tissue could then be resected until the dye became visible at the tumor boundary. Identification of the dye in the tissue was enhanced with the use of the operating microscope. The 3-dimensional position of the dye track could be determined at the end of tumor resection and compared with its initial position giving a good estimate of local brain shift. The method has proved especially helpful for the resection of large gliomas allowing for a more radical operative result.

Aged↗

PubMed1999

Growth of precultured human glioma specimens in nude rat brain.

OBJECT: The aim of this study was to develop an improved animal model for brain tumor study. The need for better and more relevant brain tumor models is generally acknowledged. Glioma tissue can be cultured directly from the biopsy specimen as tumor spheroids. Using such precultured tissue, a new in vivo model for studying human gliomas was established. METHODS: Precultured small tumor spheroids (< 300 microm) prepared from cell lines or tumor biopsy fragments were injected into the brains of immunodeficient rats by using a 5-microl Hamilton syringe that had a piston in the needle. Tumors could be established by injecting a single spheroid derived from the U-87MG cell line, whereas inoculation of 10 spheroids resulted in a tumor take comparable to that attained with injection of 10(6) single cells. Biopsy specimens obtained from six patients who underwent surgery for glioblastoma multiforme were cultured as organotypic spheroids for 11 to 18 days before inoculation into the rats. The animals were killed 3 months after spheroid implantation. Microscopic examination revealed tumor growth in 87.5 to 100% of the animals inoculated with tumor spheroids from all but one of the tumor biopsy specimens. Extensive invasion and cell migration along the nerve tracts of the corpus callosum was found in tumors that originated from four of the six biopsy specimens. CONCLUSIONS: This approach, in which spheroids from precultured biopsy specimens are injected into the brains of immunodeficient animals, provides new means for experimental studies of human malignant brain tumors in a clinically relevant animal model.

Animals↗

PubMed1998

Prevalence and prognostic significance of epilepsy in patients with gliomas.

The aim of this study was to evaluate the prevalence and prognostic significance of epilepsy in 1028 patients diagnosed in the computer tomography (CT) era with histological low- or high-grade intracranial gliomas. Survival analysis included Kaplan-Meier plots, log-rank tests, logistic regression and Cox's analysis as implemented in the SPSS statistical package. Epilepsy was a positive univariate (P < 0.0001) and multivariate, (P < 0.03) prognostic factor for survival in the total patient group (n = 1028, relative risk of death 0.83, 95% confidence interval (CI) 0.70-0.98) as well as in the high-grade patient group (n = 649, relative risk of death 0.80, 95% CI 0.66-0.96), but not in the group of low-grade glioma patients (P > 0.2). The prevalence of epilepsy in glioblastoma patients was 251/512 (49%), 95/137 (69%) in anaplastic gliomas, and 322/379 (85%) in patients with low-grade gliomas, with 97 of the 102 T1 low-grade subgroup (95%) having epilepsy, indicating that the presence of epilepsy may select patients for early radiological diagnosis. The frequency of epilepsy at presentation decreased with age in high-grade glioma patients, and increased with age in low-grade glioma patients to a plateau in the fourth decade of life (P < 0.01). The prevalence of epilepsy in patients with histological intracranial gliomas varied with patient age and tumour histology, with low-grade patients having the highest prevalence. Epilepsy was a significant positive prognostic factor except in patients with low-grade gliomas, and may select low-grade patients for early diagnosis.

Adolescent↗

PubMed1998

Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma.

UNLABELLED: We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n = 516) and low-grade (n = 315) histology. In the present report, a negative prognostic factor is associated with shortened survival. METHODS: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalen's linear model as implemented in SPSS and S-PLUS. RESULTS: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3-4), anaplastic (Grade 3), and low-grade (Grade 1-2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). CONCLUSION: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.

Adult↗

PubMed1997

Incorporation of ultrasonic imaging in an optically coupled frameless stereotactic system.

Frameless stereotactic interactive tracking systems relate a point in the surgical field to a corresponding point on the patients MR or CT scans in multiple planes. A basic weakness with these systems is that they cannot compensate for movement of target points due to brain shift caused by CSF drainage or lesion removal. Real time images can be obtained using ultrasonic techniques but the poor quality and definition and the ill-defined scan plane make interpretation difficult and reduce the usefulness of this modality. The authors have combined these two modalities by mounting light emitting diodes (LEDs) on the ultrasonic probe, thus allowing a "virtual tip" to be developed in the centre of the ultrasonic beam, and tracked via an optically coupled frameless stereotactic system (Radionics, OTS). This has allowed a direct correlation between pre-operative MR and the per-operative ultrasonic images using reformatted MR images. Ultrasound images are obtained through a separate skull opening and the image plane is determined by the position of the virtual tip. The ultrasonic and MR images are presented side by side for visual comparison. Minimally invasive tumour resection or haematoma removal could be carried out under ultrasonic guidance with direct interactive relation to the preoperative MR scans. Alternatively interactive image directed surgical procedures can be up-dated in real time by dynamic ultrasonic images taken in clearly defined scan planes.

Brain Mapping↗

PubMed1997

Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.

PURPOSE: We report survival, prognostic factors, and treatment efficacy in low-grade glioma. PATIENTS AND METHODS: A total of 379 patients with histologic intracranial low-grade glioma received post-operative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Overall survival and prognostic factors were evaluated with the SPSS statistical program (SPSS Inc, Chicago, IL). RESULTS: Median survival (all patients) was 100 months (95% confidence interval [CI], B7 to 113); in age group 0 to 19 years (n = 41), 226 months; in age group 20 to 49 years (n = 263), 106 months; in age group 50 to 59 years (n = 49), 76 months; and for older patients (n = 26), 39 months. Projected survival at 10 and 15 years was 42% and 29%, respectively. Patient age, World Health Organization (WHO) performance status, tumor computed tomography (CT) contrast enhancement, mental changes, or initial corticosteroid dependency were significant independent prognostic factors (p < .05), while histologic subgroup, focal deficits, presence of seizures, prediagnostic symptom duration, tumor category, and tumor stage were not. Patients aged 20 to 49 years with no independent negative prognostic factors (n = 132) had a median survival time of 139 months versus 41 months in patients with two or more factors (n = 33). Patients who presented with symptoms of expansion (n = 97) survived longer when resected (P < .03); otherwise no survival benefit was associated with initial tumor resection compared with biopsy. Intraarterial chemotherapy and radiation doses more than 55 Gy were not associated with prolonged survival. Among 66 reoperated patients, 45% progressed to high-grade histology within 25 months. CONCLUSION: Prognosis in low-grade glioma following postoperative radiotherapy seems largely determined by the inherent biology of the glioma and patient age at diagnosis.

Adolescent↗

PubMed1996

[Prognosis in primary tumors of the central nervous system. A patient material from the Norwegian Radium Hospital 1960-94].

We present the results of a retrospective survey of 1,218 patients treated at the Norwegian Radium Hospital during the years 1980-94 for primary tumours of the central nervous system. Median survival for patients with glioblastoma (n = 492) was 12 months, for patients with anaplastic astrocytoma (n = 83) 25 months, astrocytoma (n = 260) 95 months, oligodendroglioma (n = 85) 74 months, mixed glioma (n = 68) 65 months, and medulloblastoma (n = 53) 109 months. Median survival for patients with brain stem tumours (n = 37) was nine months, while 74% of patients with tumours in the pineal region (n = 38) survived for five years. The histology and localisation of the tumour, as well as age and functional status, are important prognostic factors for survival in patients with primary CNS tumours.

Adolescent↗

PubMed1996

Interactive image directed neurosurgery: patient registration employing the Laitinen stereo-adapter.

Fiducial markers visible on both imaging scans and the patient are a convenient and accurate method to register the patients head in stereotactic space preceeding an interactive image directed neurosurgical procedure. We have been using the Laitinen non-invasive relocatable stereo-adapter to carry the fidcucial markers both during the imaging and patient registration process. Since the adapter can be accurately remounted the surgical procedure can take place at any time interval after the imaging study. To compare registration accuracy studies were performed using a phantom carrying both surface fiducial markers and fiducial markers mounted on the stereo adapter. We have found that total system accuracy using either surface or adapter mounted markers and an optical tracking system is in the range of 3-5 mm and is acceptable for a broad range of neurosurgical applications.

Contrast Media↗