The primary sensorimotor cortex of the adult brain is capable of significant reorganization of topographic maps after deafferentation and de-efferentation. Here we show that patients with spinal cord injury exhibit extensive changes in the activation of cortical and subcortical brain areas during hand movements, irrespective of normal (paraplegic) or impaired (tetraplegic patients) hand function. Positron emission tomography ([15O]-H2O-PET) revealed not only an expansion of the cortical 'hand area' towards the cortical 'leg area', but also an enhanced bilateral activation of the thalamus and cerebellum. The areas of the brain which were activated were qualitatively the same in both paraplegic and tetraplegic patients, but differed quantitatively as a function of the level of their spinal cord injury. We postulate that the changes in brain activation following spinal cord injury may reflect an adaptation of hand movement to a new body reference scheme secondary to a reduced and altered spino-thalamic and spino-cerebellar input.

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Reorganization of human brain function after spinal cord injury (SCI) has been shown in electrophysiological studies. However, it is less clear how far changes of brain activation in SCI patients are influenced by the extent of SCI (neuronal lesion) or the consequent functional impairment. Positron emission tomography ([15O]-H2O-PET) was performed during an unilateral hand movement in SCI patients and healthy subjects. SCI patients with paraplegia and normal hand function were compared to tetraplegic patients with impaired hand movements. Intergroup comparison between paraplegic patients and healthy subjects showed an increased activation of contralateral sensorimotor cortex (SMC), contralateral thalamus, ipsilateral superior parietal lobe, and bilateral cerebellum. In contrast to this, tetraplegic patients with impaired upper limb function revealed only a significant activation of supplementary motor area (SMA). Correlational analysis in the tetraplegic patients showed that the strength of hand movement was related to the activation of contralateral SMC. However, the severity of upper limb sensorimotor deficit was related to a reduced activation of contralateral SMA and ipsilateral cerebellum. The findings suggest that in paraplegic patients with normal hand function the spinal neuronal lesion itself induces a reorganization of brain activation unrelated to upper limb function. Compared to this, in tetraplegic patients changes of brain activation are related to the impaired upper limb function. Therefore, in patients with SCI a differential impact of spinal lesion and functional impairment on brain activation can be shown. The effect of impaired afferent feedback and/or increased compensatory use of non-impaired limbs in SCI patients needs further evaluation.

(MR). A homogeneous population of 11 patients with progressive non-enhancing LGG was prospectively studied. Imaging was done at 6-months intervals starting six months, and in a second series starting three months after treatment initiation. F-18 fluoro-ethyl-l-tyrosine (FET) uptake was quantified with PET as metabolically active tumor volume, and was compared with the tumor volume on MR. Response was defined as ≥10% reduction of the initial tumor volume. Eight patients showed metabolic responses. Already 3 months after start of chemotherapy the active FET volumes decreased in 2 patients to a mean of 44% from baseline. First MR volume responses were noted at 6 months. Responders showed a volume reduction to 31 ± 23% (mean ± SD) from baseline for FET, and to 73 ± 26% for MR. The time to maximal volume reduction was 8.0 ± 4.4 months for FET, and 15.0 ± 3.0 months for MR. The initial metabolic response correlated with the best volume response on MR (Spearman Rank P = 0.011). Deactivation of amino acid transport represents an early indicator of chemotherapy response in LGG. Response assessment based on MR only has to be reconsidered. The time window obtained from PET may assist for individual treatment decisions in LGG patients. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Wyss page 2 AbstractBackground: Amino acid transport and protein synthesis are important steps of tumor

We used positron emission tomography (PET) with [18F]fluoromisonidazole ([18F]FMISO) to study tumor hypoxia in six dogs with spontaneous sarcomas. The tumors were regarded as hypoxic if [18F]FMISO uptake exceeded normal tissue radioactivity by 40% (tumor/muscle ratio > 1.4) or if kinetic analysis indicated a positive [18F]FMISO tissue influx rate (Ki > 0) by a Patlak plot. Using these criteria, we found hypoxia in a fibrosarcoma grade II, an undifferentiated sarcoma, and an ostoeosarcoma, but not in a fibrosarcoma grade I, another osteosarcoma, and a myxosarcoma. In three animals, the tumor oxygen partial pressure (pO2) was also measured invasively using Eppendorf needle electrodes. In these cases, the Eppendorf measurements were confirmed by the [18F]FMISO PET results. In addition, [15O]H2O PET was performed in four dogs in order to assess tumor perfusion. Comparisons of the [18F]FMISO with [15O]H2O PET images in two cases showed that tumor hypoxia occurred in the tumor center with low perfusion, whereas perfusion was heterogeneous in a nonhypoxic tumor.

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The differential diagnosis of single space-occupying lesions comprises multiple sclerosis (MS) in younger patients and primary or secondary brain tumour at any age. We describe a 70-year-old man with recurrent tumour-like intracerebral masses, which were diagnosed as tumefactive demyelination (TD). He presented with confusion, headache and hemineglect. Past medical history included coronary heart disease and atrial fibrillation. Magnetic resonance imaging (MRI) of the brain revealed a single right parieto-occipital lesion (Fig. 1a, d). Search for primary neoplasm (lymph nodes, blood cell analysis, computer tomography of the thorax and abdomen, and whole body deoxyglucose positron emission tomography) was negative. The cerebrospinal fluid including fluorescenceactivated cell sorter showed mild lymphocytic pleocytosis (27 cells/ll) and elevated protein (0.71 g/l), but no oligoclonal bands or tumour cells. Biopsy of the cerebral lesion showed foamy macrophages and focal perivascular lymphocytic cuffs, which are indicative of demyelination ( Fig. 1g-j). There was no evidence of a neoplasm. Following biopsy the patient rapidly improved to a course of oral dexamethasone starting with 12 mg per day. Six and 12 weeks later his MRI showed substantial regression of the lesion with residual non-space-occupying hyperintensity on T2-weighted MRI. Eight, 23 and 29 months later, the patient developed single symptomatic lesions again (representative images are shown in Fig. 1b, c, e and f). He again responded to oral dexamethasone, and clinical improvement was paralleled by a decrease of lesion volume and contrast enhancement on MRI. Repeated extensive search for a primary tumour was negative. Ten months after the initial presentation of TD the patient presented with adynamia, anaemia and leukopaenia. Bone marrow examination revealed myelodysplastic syndrome (MDS). Eleven months later the patient suffered from haematuria, which led to the diagnosis of renal cell carcinoma. He died 34 months after the first manifestation of TD due to metastatic renal cancer. Brain autopsy findings were similar to those of the biopsy. Again, there was no evidence of lymphoma or any other neoplastic process. Our final diagnosis was recurrent TD.Our patient developed four single tumour-like lesions at various sites of the brain over 3 years. There was no preceding viral infection or vaccination. From the initial appearance on MRI, central nervous system lymphoma was suggested. However, neither biopsy nor autopsy revealed tumour. Age, clinical course with recurrent single lesions and negative oligoclonal bands in our patient suggest that at least a subset of TD cases may represent a distinct entity rather than a manifestation of MS [1]. In our case the diagnosis of MS appears very unlikely. Based on the

Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by increased tumor cellularity and angiogenesis. We used diffusion-weighted MR imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2-18 F-fluorethyl)-L-tyrosine ( 18 F-FET) to search for focal changes of diffusion (ADC) and amino acid uptake and to investigate whether focal changes in these parameters colocalize within LGGs. Methods: We retrospectively selected 18 patients with nonenhancing LGG. All patients had undergone 18 F-FET PET and MR imaging for preoperative evaluation or for therapy monitoring in recurrent or progressive LGG. Region-of-interest analysis was performed to compare 18 F-FET uptake and ADC values in areas with focal intratumoral maximum metabolic activity and diffusion restriction and between tumor and normal brain. 18 F-FET uptake was normalized to the mean cerebellar uptake (ratio). ADC values were also compared with the 18 F-FET uptake on a voxel-by-voxel basis across the whole tumor. Results: The mean focal maximum (mean ± SD, 1.69 ± 0.85) and global 18 F-FET uptake in tumors (1.14 ± 0.41) exceeded that of normal cortex (0.85 ± 0.09) and cerebrospinal fluid (0.82 ± 0.20). ADC values in the area with most restricted diffusion (1.07 ± 0.22 · 10 −3 mm 2 /s) and in the whole tumor (1.38 ± 0.27 · 10 −3 mm 2 /s) were in the range between normal cortex (0.73 ± 0.06 · 10 −3 mm 2 /s) and cerebrospinal fluid (2.84 ± 0.09 · 10 −3 mm 2 /s). 18 F-FET uptake did not correlate with corresponding (colocalizing) ADC values, either in the area with focal maximum metabolic activity or in the area with most restricted diffusion or in the whole tumor. Conclusion: There is no congruency between 18 F-FET uptake and diffusivity in nonenhancing LGG. Diffusion restriction in these tumors most likely represents changes in brain and tumor cell densities as well as alteration of water distribution and is probably not directly correlated with the density of tumor cells.