Pharmacokinetics and dose estimates following intrathecal administration of 131I-monoclonal antibodies for the treatment of central nervous system malignancies.

PURPOSE: Treatment of malignant disease in the central nervous system (CNS) with systemic radiolabeled monoclonal antibodies (MoAbs) is compromised by poor penetration into the cerebrospinal fluid (CSF), limited diffusion into solid tumors, and the generation of anti-mouse antibodies. To attempt to avoid these problems we have treated patients with diffuse neoplastic meningitis with radioimmunoconjugates injected directly into the intrathecal space. METHODS AND MATERIALS: Tumor-specific MoAbs were conjugated to Iodine-131 (131I) (629-3331 MBq) by the Iodogen technique, and administered via an intraventricular reservoir. A clinical response rate of approximately 33% was achieved, with better results in more radiosensitive tumors. Here, we present detailed pharmacodynamic data on patients receiving this intracompartmental targeted therapy. RESULTS: Elimination from the ventricular CSF appeared biphasic, with more rapid clearance occurring in the first 24 h. Radioimmunoconjugate entered the subarachnoid space and subsequently the vascular compartment. From this information, the areas under the effective activity curves for ventricular CSF, blood, and subarachnoid CSF were calculated to permit dosimetry. Critical organ doses were calculated using conventional medical internal radiation dose (MIRD) formalism. Where available, S-values were taken from standard tables. To calculate the doses to CSF, brain, and spinal cord, S-values were evaluated using the models described in the text. CONCLUSION: A marked advantage could be demonstrated for the dose delivered to tumor cells within the CSF as compared to other neural elements.

Design and evaluation of a system for microscope-assisted guided interventions (MAGI).

The problem of providing surgical navigation using image overlays on the operative scene can be split into four main tasks--calibration of the optical system; registration of preoperative images to the patient; system and patient tracking, and display using a suitable visualization scheme. To achieve a convincing result in the magnified microscope view a very high alignment accuracy is required. We have simulated an entire image overlay system to establish the most significant sources of error and improved each of the stages involved. The microscope calibration process has been automated. We have introduced bone-implanted markers for registration and incorporated a locking acrylic dental stent (LADS) for patient tracking. The LADS can also provide a less-invasive registration device with mean target error of 0.7 mm in volunteer experiments. These improvements have significantly increased the alignment accuracy of our overlays. Phantom accuracy is 0.3-0.5 mm and clinical overlay errors were 0.5-1.0 mm on the bone fiducials and 0.5-4 mm on target structures. We have improved the graphical representation of the stereo overlays. The resulting system provides three-dimensional surgical navigation for microscope-assisted guided interventions (MAGI).

The implementation of postgraduate training programs through state and local resources.

A profile of implementation strategies for funding postgraduate training programs using local or state resources is described. The need for those implementation strategies as well as basic principles for successful implementation is documented. Two programs are briefly described--a University Affiliated Program (UAP) in western New York and a UAP in Missouri--as the basis for generating implementation strategies. Finally a discussion is provided reviewing the strengths and weaknesses of these strategies.

Acoustic schwannoma.

Acoustic schwannomas are the commonest tumours of the cerebellopontine angle and usually present with unilateral deafness. Earlier diagnosis while the tumour is small, coupled with surgical treatment by a specialized neuro-otology team, has contributed to a significant decrease in the mortality and morbidity due to these tumours.

Initial assessment and management of the severely head-injured patient.

Head injuries account for a significant proportion of acute hospital admissions. The first few hours after a serious head injury are extremely important, particularly in terms of reducing possible secondary injuries. This article addresses the management problems in this group of patients during this initial critical period.

Persistent absence of ring-enhancement on CT with an encapsulated brain abscess.

Ring-enhancement on CT (RECT) is generally considered a sine qua non in diagnosing a cerebral abscess. We describe a 16-year-old female who presented with headaches, vomiting and drowsiness, which over 2 weeks rapidly progressed to coma. CT demonstrated a moderately large left frontal extradural abscess, associated with contiguous left frontal osteomyelitis, and underlying frontal and ethmoidal sinusitis. In addition, there was a large circular low density area within the left frontal lobe associated with midline shift that, owing to negative RECT, was assumed to represent nascent ischaemic cerebritis. Despite emergency twist-drill drainage of the extradural abscess, and antibiotic/corticosteroids administration, her clinical condition continued to deteriorate and two episodes of uncal herniation were reversed medically. Repeated CT, however, continued to demonstrate negative enhancement within the left frontal low density, although significant enhancement continued to be apparent with recurrent contiguous extradural suppuration. At definitive craniotomy, a large, well-encapsulated abscess cavity was excised from the left frontal lobe corresponding precisely to the area of previously negative enhancement, along with drainage of the recurrent extradural abscess. Thus, in addition to well-known 'false-positives' for RECT with a cerebral abscess, our case highlights the rare occurrence of a 'false-negative'. A low density mass lesion on CT with persistent negative RECT can neither be assumed to represent early cerebritis nor to exclude a mature abscess.

Imaging after titanium cranioplasty.

Titanium cranioplasty has been used in our unit for reconstruction of cranial defects following trauma, tumour resection and bone loss due to postcraniotomy infection. It has previously been assumed that imaging to assess recurrence of disease progression after cranioplasty would be severely compromised in the presence of metallic material. Titanium is a non-ferrous metal of low atomic number, which is relatively radiolucent and allows exceptionally clear images to be obtained without significant degradation of image quality, on CT and magnetic resonance (MR) imaging. Cases are presented that demonstrate the use of CT contrast cisternography and MR imaging after titanium cranioplasty. On the basis of its strength, biocompatibility and excellent handling characteristics, allied to its suitability for all post-operative imaging techniques, we conclude that titanium plate is the material of choice for cranioplasty.

Primary spinal malignant schwannoma.

Malignant schwannomas are uncommon primary tumours of nerve sheath origin. They are rarely found within the spine and spinal canal, and little is known about their management in this unusual location. We describe the presentation of three patients with primary spinal malignant schwannomas and discuss the surgical management.

A system for microscope-assisted guided interventions.

We present a system for surgical navigation using stereo overlays in the operating microscope aligned to the operative scene. This augmented reality system provides 3D information about nearby structures and offers a significant advancement over pointer-based guidance, which provides only the location of one point and requires the surgeon to look away from the operative scene. With a previous version of this system, we demonstrated feasibility, but it became clear that to achieve convincing guidance through the magnified microscope view, a very high alignment accuracy was required. We have made progress with several aspects of the system, including automated calibration, error simulation, bone-implanted fiducials and a dental attachment for tracking. We have performed experiments to establish the visual display parameters required to perceive overlaid structures beneath the operative surface. Easy perception of real and virtual structures with the correct transparency has been demonstrated in a laboratory and through the microscope. The result is a system with a predicted accuracy of 0.9 mm and phantom errors of 0.5 mm. In clinical practice errors are 0.5-1.5 mm, rising to 2-4 mm when brain deformation occurs.