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.

Seventeen patients with presumed glial brain tumors were examined with proton chemical shift imaging and single voxel spectroscopy that used different echo times. Metabolite resonances were evaluated by metabolic ratios and absolutely by correcting for coil load and comparison to phantom measurements. Metabolic images were created to visualize the metabolic changes. All patients showed spectra that were different from those measured in healthy control subjects. Spectral changes were also present in normal-appearing matter (NAM) that was distant from lesions. The resonance at 3.55 ppm which is usually assigned to both myo-inositol and glycine, was the only one to allow a discrimination between healthy volunteers, astrocytoma grade II, and glioblastoma multiforme (GBM) (p < 0.02). From the different echo times used we conclude that an increase in this resonance has to be assigned to glycine rather than myo-inositol. This resonance might be used to grade human gliomas more reliably. Total creatine (Cr) decreased more drastically with malignancy than N-acetylated metabolites (NA). This led to a higher NA/Cr ratio in GBM compared to astrocytoma grade II. NA/Cr was thus pseudonormal in GBM due to a change in both nominator and denominator. This study reveals the importance of comparing magnetic resonance spectroscopy data of lesions to spectra measured in identical localizations in healthy control subjects instead of NAM and the importance of quantifying single metabolic peaks instead of creating metabolic ratios in clinical magnetic resonance spectroscopy.

Several multi-dimensional statistical evaluation methods were applied to single-voxel proton MR spectra of glial brain tumors and of healthy volunteers. Metabolic coordinates with histological relevance for future diagnosis were found by which spectra from controls, low-grade tumors, and high-grade tumors were completely separated. Significant differences between low-grade and high-grade glioma patients and controls were found for several metabolic ratios by variance analysis. Cluster analysis both with and without principal component analysis was applied. The outcome of these two approaches depended mainly on the lipid-to-creatine ratio. Two other approaches, discriminant factor analysis and the orthonormal discriminant vector method were then used to find discriminatory metabolic coordinates. It turned out that a linear combination of all evaluable metabolic ratios made it possible to separate the three groups completely. On the basis of these results, a classification method that uses the entire proton MRS spectrum is proposed.

Localized short echo time (TE = 20 ms), stimulated echo acquisition mode, and double spin echo (TE = 135 ms) proton spectroscopy were performed in clearly defined, acute Gadolinium (Gd)-enhancing multiple sclerosis (MS) plaques of 22 patients with clinically definite MS. The resonances of N-acetylated metabolites (NA), creatine/phosphocreatine (Cr), choline-containing compounds (Cho), glycine/myo-inositol (Ino), and lactate were evaluated. The ratios of NA/Cr and NA/Cho were significantly decreased, Cho/Cr increased, and Ino/Cr remained unchanged. No marker peaks or elevated lactate levels were found. The measured metabolic changes were practically independent of the relative plaque size within the volume of interest (8 ml). Thus, the spectral changes measured with 1H MRS in acute Gd-enhancing MS plaques originate not only from the lesion as depicted by MRI, but also from the surrounding normal-appearing white matter.