The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin. Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metablic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in chronic schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.

Since the end of 1996, we have treated more than 160 patients at PSI using spot-scanned protons. The range of indications treated has been quite wide and includes, in the head region, base-of-skull sarcomas, low-grade gliomas, meningiomas, and para-nasal sinus tumors. In addition, we have treated bone sarcomas in the neck and trunk--mainly in the sacral area--as well as prostate cases and some soft tissue sarcomas. PTV volumes for our treated cases are in the range 20-4500 ml, indicating the flexibility of the spot scanning system for treating lesions of all types and sizes. The number of fields per applied plan ranges from between 1 and 4, with a mean of just under 3 beams per plan, and the number of fluence modulated Bragg peaks delivered per field has ranged from 200 to 45 000. With the current delivery rate of roughly 3000 Bragg peaks per minute, this translates into delivery times per field of between a few seconds to 20-25 min. Bragg peak weight analysis of these spots has shown that over all fields, only about 10% of delivered spots have a weight of more than 10% of the maximum in any given field, indicating that there is some scope for optimizing the number of spots delivered per field. Field specific dosimetry shows that these treatments can be delivered accurately and precisely to within +/-1 mm (1 SD) orthogonal to the field direction and to within 1.5 mm in range. With our current delivery system the mean widths of delivered pencil beams at the Bragg peak is about 8 mm (sigma) for all energies, indicating that this is an area where some improvements can be made. In addition, an analysis of the spot weights and energies of individual Bragg peaks shows a relatively broad spread of low and high weighted Bragg peaks over all energy steps, indicating that there is at best only a limited relationship between pencil beam weighting and depth of penetration. This latter observation may have some consequences when considering strategies for fast re-scanning on second generation scanning gantries.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

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