The right inferior frontal gyrus and poststroke aphasia: a follow-up investigation.

BACKGROUND AND PURPOSE: Recently, a combined repetitive transcranial magnetic stimulation (rTMS) and activation positron emission tomography (PET) study showed essential language function of the right inferior frontal gyrus (IFG) in some right-handed acute poststroke aphasics. We reexamined these patients in the chronic phase to test whether the right IFG remained essential for language performance. METHODS: We reexamined 9 male right-handed patients, age 41 to 75 years, with aphasia 8 weeks after left hemispheric stroke. rTMS was performed over the maximum activation within the left and right IFG as defined by (15)[O]water PET to interfere with language function. A positive rTMS effect was defined as increased reaction time latency or error rate in the semantic task relative to no stimulation. RESULTS: PET activations of the IFG were observed on the left (2 patients) and bilaterally (7). During rTMS interference over the left IFG, all patients had positive TMS effects, indicating that the left IFG remained essential. Stimulation over the right IFG yielded positive rTMS effects in 2 patients with persisting right IFG activation. Two patients with positive rTMS effects over the right side in the initial study did not show these effects at follow-up. Language performance improved in all patients. CONCLUSIONS: Successful regeneration from poststroke aphasia seems to depend more on the integration of available language-related brain regions than on recruiting new brain regions during the rehabilitation process. Restoration of the left hemisphere network seems to be more effective, although in some cases, right hemisphere areas are integrated successfully.

Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia: a combined repetitive transcranial magnetic stimulation and positron emission tomography study.

BACKGROUND AND PURPOSE: Functional neuroimaging studies have demonstrated right inferior frontal gyrus (IFG) activation in poststroke aphasia. It remains unclear whether this activation is essential for language performance. We tested this hypothesis in a positron emission tomography (PET) activation study during a semantic task with repetitive transcranial magnetic stimulation (rTMS) on right-handed patients experiencing poststroke aphasia and examined whether rTMS stimulation over the right and left IFG would interfere with language performance. METHODS: Eleven patients with left-sided middle cerebral arterial infarction, 50 to 75 years of age, were tested with the Aachen Aphasia Test Battery and underwent (15)O-H2O PET activation during a semantic task within 2 weeks after stroke. PET activation images were coregistered to T1-weighted MRIs. Stimulation sites were determined on renderings of head and brain over the maximum activation within left and right IFG. rTMS was performed with 20% maximum output (2.1 T), 10-s train duration, at 4 Hz frequency. A positive rTMS effect was defined as an increased reaction time latency or error rate in the semantic task. RESULTS: PET activations of the IFG were observed on the left (3 patients) and bilaterally (8 patients). Right IFG stimulation was positive in 5 patients with right IFG activation, indicating essential language function. In a verbal fluency task, these patients had a lower performance than patients without right-sided TMS effect. CONCLUSIONS: In some poststroke aphasics, right IFG activation is essential for residual language function. However, its compensatory potential seems to be less effective than in patients who recover left IFG function. These results suggest a hierarchy in recovery from poststroke aphasia and a (limited) compensatory potential of the nondominant hemisphere.

Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology.

PURPOSE: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. EXPERIMENTAL DESIGN: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. RESULTS: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). CONCLUSIONS: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.

Switching on the lights for gene therapy.

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application.