David G. T. Thomas

A patient‐to‐computed‐tomography image registration method based on digitally reconstructed radiographs

An automatic method for the accurate registration of computed tomography (CT) data with two camera-calibrated radiographs is presented. The registration is based on the skull as visualized both in the plain radiographs and in radiographs digitally reconstructed from CT. A reference coordinate system is established based on the radiographic projection parameters obtained using an angiographic stereotactic localizer. The CT-derived reconstructed radiographs are aligned iteratively at multiple resolutions until a best match is found by adjusting the position and orientation of the CT data set relative to the reference coordinate system. The results of experiments with a skull phantom performed under stereotactic control which show that reliable registration is possible with an accuracy better than 1 mm are presented. Possible applications include intraoperative patient-to-CT frameless registration and registration of radiographic data with frameless CT for depth electroencephalogram electrode position confirmation.

Surgical treatment of patients with single and dual pathology: Relevance of lesion and of hippocampal atrophy to seizure outcome

Article abstract-Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engels class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engels class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus. NEUROLOGY 1997;48: 437-444

Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma

Ependymomas are the third most common brain tumour in the paediatric population. Although cytogenetic and molecular analyses have pinpointed deletions of chromosomes 6q, 17, and 22 in a subset of tumours, definitive patterns of genetic aberrations have not been determined. In the present study, we analysed 40 ependymomas from paediatric patients for genomic loss or gain using comparative genomic hybridisation (CGH). Eighteen of the tumours (45%) had no detectable regions of imbalance. In the remaining cases, the most common copy number aberrations were loss of 22 (25% of tumours) and gain of 1q (20%). Three regions of high copy number amplification were noted at 1q24‐31 (three cases), 8q21‐23 (two cases), and 9p (one case). Although there was no association with the loss or gain of any chromosome arm or with benign versus anaplastic histologic characteristics, the incidence of gain of 7q and 9p and loss of 17 and 22 was significantly higher in recurrent versus primary tumours. This study has identified a number of chromosomal regions that may contain candidate genes involved in the development of different subgroups of ependymoma.

Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C]diprenorphine and positron emission tomography

The binding of [11C]diprenorphine to µ, κ, and Δ subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Measurement of blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume in human brain tumours and surrounding oedematous tissue

The blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume were measured in brain tumours and the surrounding cerebral tissues. A total of 21 patients were studied. These included 10 primary tumours, eight secondary and three with unknown histology. Measurements were performed using the oxygen-15 steady state inhalation technique and positron emission tomography. Within the tumours no relation between blood flow, oxygen utilisation and blood volume was found. In all tumours oxygen supply was in excess of the oxygen demand of the tissues as reflected in oxygen extraction ratios that were lower than those of normal brain tissue. No indication of local ischaemia in peritumour oedema was found.

Quantitative Measurement of Blood—Brain Barrier Permeability Using Rubidium-82 and Positron Emission Tomography

In normal brain, the blood–brain barrier (BBB) is highly impermeable to K+ cations, their transport being controlled by ATPases situated in the endothelial cell membranes. 82Rb+ is a positron-emitting analogue of K+ with a half-life of 75 s. Using a steady-state model and positron emission tomography, quantitative extraction data for 82Rb+ transport across the BBB have been obtained both in normal human subjects and in a variety of conditions of cerebral pathology. A mean cerebral Rb extraction of 2.1% was found for normal subjects, corresponding to a mean value of 1.1 × 10−6 cm s−1 for 82Rb+ cation permeability across the BBB. No increase in cerebral Rb extraction was observed for patients with diffusely raised intracranial pressure secondary to obstructive hydrocephalus and benign intracranial hypertension, or for patients with multiple sclerosis or cerebral systemic lupus erythematosus. Cerebral tumours that were enhanced on computed tomography scanning showed a significant increase in local Rb uptake. No correlation between tumour size, or grade of glioma, and tumour Rb extraction was found. Nonenhancing tumours showed no increase in local Rb extraction, and regions of perifocal tumour oedema also had Rb extraction values in the normal range. It is concluded that increased Rb extraction occurs only where tight junction integrity in the BBB breaks down locally, that is, in the microcirculation of enhancing tumours but not in that of perifocal regions of tumour oedema or nonenhancing tumours.

Experience in 300 Cases of CT-directed Stereotactic Surgery for Lesion Biopsy and Aspiration of Haematoma

Despite advances in imaging of the brain, an accurate diagnosis of brain lesions requires tissue sampling and histological verification. A series of CT-directed procedures has been performed in 300 patients with deep sited, multiple, diffuse, extensive, small or inflammatory lesions, brain stem haematomas and tumours presenting with epilepsy. A positive diagnosis was obtained in 271 cases (92.8%), no diagnosis in 21 cases (7.2%). Therapeutic results were also obtained in eight cases (2.7%) of brain stem haematoma aspiration. Complications occurred in 14 cases (4.7%) including one death (0.3%). Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, CT-directed stereotactic biopsy should be considered in all patients harbouring deep seated, multiple, diffuse, small or inflammatory brain lesions.

Voxel‐based localization in frame‐based and frameless stereotaxy and its accuracy

The problem of accurate stereotactic localization and registration of targets in computed tomography (CT) data sets is addressed, in particular the effect of using a single transformation matrix to map voxel coordinates onto stereotactic coordinates. An algebraic approach to the calculation of stereotactic target coordinates in tomographic data acquired with conventional stereotactic localizers is presented. The volume transformation matrix (VTM) is discussed, which is useful for the registration of volumetric data sets, and also corresponds to the rigid body transformation matrix used in many so-called frameless registration methods. The VTM can lead to accuracy degradation, in particular due to patient movement during scanning. Simulations were performed and CT data sets acquired with patients fitted with the CRW or the GTC stereotactic localizer were analyzed. Comparison of STM- and VTM-derived stereotactic coordinates shows an average overall registration error of 0.1 mm for anesthetized patients and in the range 0.6-1.4 mm for nonanesthetized patient. Accuracy maps are described that enable the user to visualize the registration error in relation to the data. It is shown that the effect of fiducial point localization error and patient movement for VTM-based localization is minimized when all available fiducials in the region of interest are used. The significance of these results is discussed, and methods are proposed to minimize these effects for frame-based and frameless registration methods.

Blood flow and oxygen utilisation in the contralateral cerebral cortex of patients with untreated intracranial tumours as studied by positron emission tomography, with observations on the effect of decompressive surgery.

Using positron emission tomography, regional cerebral blood flow and oxygen utilisation were measured in the contralateral cortex of 14 patients with a variety of intracranial tumours. A comparison was made with cortical values derived from 14 normal controls. Compared with normal subjects, patients with brain tumours had a significant reduction in oxygen utilisation and blood flow in their contralateral cortex. Decompression resulting from craniotomy and biopsy, led to a partial reversal of this cerebral hypofunction.

Accuracy in Frame-Based and Frameless Stereotaxy

Stereotactic surgery is currently undergoing great changes with a large number of frameless methodologies being developed alongside traditional frame-based systems. As a result, there is considerable uncertainty over the future clinical roles of the numerous stereotactic options now offered. We have reviewed the current scientific issues regarding accuracy in both frame-based and frameless stereotaxy. Frame-based systems have the advantage of proven clinical utility and instrument carriage with a high degree of mechanical stability and accuracy. Frameless methods are more complex, but also more flexible, and may have wide applications in general neurosurgery if clinical efficacy is confirmed.