Walter Jentzen

Arm Training Induced Brain Plasticity in Stroke Studied with Serial Positron Emission Tomography

We used serial positron emission tomography (PET) to study training-induced brain plasticity after severe hemiparetic stroke. Ten patients were randomized to either task-oriented arm training or to a control group and scanned before and after 22.6 +/- 1.6 days of treatment using passive movements as an activation paradigm. Increases of regional cerebral blood flow (rCBF) were assessed using statistical parametric mapping (SPM99). Before treatment, all stroke patients revealed bilateral activation of the inferior parietal cortex (IPC). After task-oriented arm training, activation was found bilaterally in IPC and premotor cortex, but also in the contralateral sensorimotor cortex (SMC). The control group only showed weak activation of the ipsilateral IPC. After treatment, the training group revealed relatively more activation bilaterally in IPC, premotor areas, and in the contralateral SMC. Five normal subjects showed no statistical significant differences between two separate PET studies. In this group of patients, task-oriented arm training induced functional brain reorganization in bilateral sensory and motor systems.

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

Cortical Activation to Auditory Mismatch Elicited by Frequency Deviant and Complex Novel Sounds: A PET Study

The analysis of auditory deviant events outside the focus of attention is a fundamental capacity of human information processing and has been studied in experiments on Mismatch Negativity (MMN) and the P3a component in evoked potential research. However, generators contributing to these components are still under discussion. Here we assessed cortical blood flow to auditory stimulation in three conditions. Six healthy subjects were presented with standard tones, frequency deviant tones (MMN condition), and complex novel sounds (Novelty condition), while attention was directed to a nondemanding visual task. Analysis of the MMN condition contrasted with thestandard condition revealed blood flow changes in the left and right superior temporal gyrus, right superior temporal sulcus and left inferior frontal gyrus. Complex novel sounds contrasted with the standard condition activated the left superior temporal gyrus and the left inferior and middle frontal gyrus. A small subcortical activation emerged in the left parahippocampal gyrus and an extended activation was found covering the right superior temporal gyrus. Novel sounds activated the right inferior frontal gyrus when controlling for deviance probability. In contrast to previous studies our results indicate a left hemisphere contribution to a frontotemporal network of auditory deviance processing. Our results provide further evidence for a contribution of the frontal cortex to the processing of auditory deviance outside the focus of directed attention.

Value of 124I-PET/CT in staging of patients with differentiated thyroid cancer

The aim of this study is to evaluate the clinical significance of 124I positron emission tomography (PET) using a combined PET/CT tomograph in patients with differentiated thyroid carcinoma and to compare the PET/CT results with 131I whole-body scintigraphy (WBS), dedicated PET and CT alone. Twelve thyroid cancer patients were referred for diagnostic workup and entered complete clinical evaluation, including histology, cytology, thyroglobulin level, ultrasonography, fluorine-18 fluorodeoxyglucose (FDG)-PET, FDG-PET/CT and CT. Lesion-based evaluation showed a lesion delectability of 56, 87 and 100% for CT, 124I-PET, and combined 124I-PET/CT imaging, respectively. Lesion delectability of 131I-WBS was 83%. We conclude that 124I-PET/CT imaging is a promising technique to improve treatment planning in thyroid cancer. It is particularly valuable in patients suffering from advanced differentiated thyroid cancer prior to radio-iodine therapy and in patients with suspected recurrence and potential metastatic disease.

Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [(15)O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.

Optimized 124I PET Dosimetry Protocol for Radioiodine Therapy of Differentiated Thyroid Cancer

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. Methods: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20–40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (≤5 Gy GBq−1; n = 14), medium (between 5 and 10 Gy GBq−1; n = 9), or high LDpAs (>10 Gy GBq−1; n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lins concordance correlation coefficient (ρc) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. Results: The effective 124I half-life, linear activity–concentration rate (α), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a ρc value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. Conclusion: Lesion classification into LDpA groups was feasible using a single PET scan at ∼24 h. Because of the highly variable kinetics, 1 additional measurement at ∼96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.

Dual Modality of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Patients with Cervical Carcinoma of Unknown Primary

Objective: To evaluate an optimized F-18-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquisition protocol for head and neck cancer and assess the usefulness of combined FDG-PET/CT in locating unknown primary tumors in patients with biopsy-proven cervical lymph node metastases. Subjects and Methods: Twenty-one patients with cervical lymph node metastases of unknown primary tumors underwent staging with FDG-PET/CT. The images of FDG-PET alone, CT alone, FDG-PET/CT read side by side and fused and FDG-PET/CT were evaluated separately by 2 physicians. Imaging results were correlated with either histology (n = 14) or clinical follow-up (n = 7). Results: On the fused FDG-PET/CT images, primary tumors were identified in 12 patients (57%); with FDG-PET alone and FDG-PET and CT read side by side 11 (52%) primary tumors were found while CT alone identified 5 (23%) primary tumors. Conclusion: Our data indicate that fused FDG-PET and CT images increased the sensitivity of detecting carcinoma of unknown primary (CUP) tumors compared to CT alone, but not to FDG-PET alone or FDG-PET and CT read side by side. Hence accurate fusion of functional and morphologic data by FDG-PET/CT is a promising imaging modality in the clinical workup of patients with cervical CUP tumors.

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

PurposeBy targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUVmax) and sst mRNA.MethodsA total of 120 patients were subjected to diagnostic 68Ga-DOTATOC positron emission tomography (PET)/CT (age range 19–83 years). SUVmax values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1–sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR).ResultsSUVmax revealed a region-specific pattern (e.g., mean ± SD, spleen 31.1 ± 10.9, kidney 16.9 ± 5.3, liver 12.8 ± 3.6, stomach 7.0 ± 3.1, head of pancreas 6.2 ± 2.3, small bowel 4.8 ± 1.8, thyroid 4.7 ± 2.2, bone 3.9 ± 1.3, large bowel 2.9 ± 0.8, muscle 2.1 ± 0.5, parotid gland 1.9 ± 0.6, axillary lymph node 0.8 ± 0.3 and lung 0.7 ± 0.3). SUVmax was age independent. Gender differences were evident within the thyroid (female/male: 3.7 ± 1.6/5.5 ± 2.4, p < 0.001; Mann-Whitney U test) and the pancreatic head (5.5 ± 1.9/6.9 ± 2.2, p < 0.001). The sst mRNA was widely expressed and heterogeneous, showing sst1 to be most abundant. SUVmax values exclusively correlated with sst2 expression (r = 0.846, p < 0.001; Spearman rank correlation analysis), whereas there was no correlation of SUVmax with the expression of the other four subtypes.ConclusionIn normal human tissues 68Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis.

Dorsolateral prefrontal cortex activation during automatic auditory duration-mismatch processing in humans: a positron emission tomography study

This study aimed to identify the neural networks underlying automatic and active auditory deviant detection in six healthy subjects using positron emission tomography. Eight alternating blocks of standard and standard plus duration-deviant tones were presented while subjects performed a visual discrimination task. In an additional four blocks, the subjects then performed an auditory discrimination task on the deviant tones. Actively attending the deviant tones increased regional cerebral blood flow (rCBF) in the superior temporal and inferior frontal gyrus as well as in the superior and medio-frontal gyrus. When performing the visual task and presented with deviant tones, significant increase of rCBF was detected in the caudate nucleus, cerebellum, posterior cingulate, inferior frontal and pre-central gyrus thus indicating automatic extra-pyramidal processing of auditory duration deviants.

Clinical applications of 124I-PET/CT in patients with differentiated thyroid cancer

Abstract124I-PET/CT has a high clinical potential in patients with differentiated thyroid cancer (DTC). Two aspects deserve special mention: staging of recurrent or residual disease and pretherapy dosimetry. Used in combination 124I-PET and CT allows foci of highly specific 124I uptake to be localized with a low radiation dose, which is specifically important in pretherapy diagnostics. In addition in the combination of FDG-PET and CT non-iodine-avid lesions may be detected and may be discriminated from simultaneously occurring iodine-positive lesions. In clinical applications, the pretherapy 124I-PET dosimetry may result in a significant alteration in the therapeutic procedure compared to standard therapy using fixed therapeutic activities. In this context, 124I-PET dosimetry is a useful procedure especially in advanced DTC, and allows the administration of safer and more effective radioiodine activities as well as earlier multimodal interventions compared to standard empirical protocols. This review summarizes the clinical data on 124I-PET/CT in patients with DTC, and addresses future prospects.