Karl-Titus Hoffmann

Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging?

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and 18F-FDG-PET (n=23) before and 2–4xa0weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60±14%) was significantly higher than in nonresponders (37±31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

Restaging of Locally Advanced Carcinoma of the Rectum with MR Imaging after Preoperative Radio-Chemotherapy plus Regional Hyperthermia

Background: The restaging accuracy of MR imaging in advanced primary rectal carcinoma after preoperative radiochemotherapy and regional hyperthermia was evaluated and compared with the histopathologically verified degree of tumor remission after a course of radio-chemo-thermotherapy.nn Patients and Methods: 35 patients with primary rectal carcinoma (uT3/uT4) underwent MRI using a surface coil 4–6 weeks after radiochemotherapy (n = 35), regional hyperthermia (n = 23), and before curative surgery. We defined as gold standard for the remission status the comparison of pretherapeutic endosonography with the histopathology of the resected specimen.nn Results: T category was correctly restaged after preoperative treatment in only 19 (54%) of 35 patients. Nine of 20 responders were overstaged and seven of 15 non-responders were understaged. Concurrently, the N category was correctly restaged in 19 (54%) of 35 patients (twelve responders and seven non-responders). Overstaging occurred in four responders and two non-responders, understaging occurred in four responders and six non-responders.nn Conclusions: MRI proved independent of the response status as not suitable to restage locally advanced rectal carcinoma after preoperative radiochemotherapy despite optimized imaging technique and spatial resolution. Basically, imaging the morphology of a tumor cannot clearly differentiate between vital and devitalized tissue after a treatment. Functional imaging such as PET (positron emission tomography) appears more feasible for restaging after radio-chemo-thermotherapy.Hintergrund: Die Genauigkeit der Stadienbestimmung mittels MR-Bildgebung wurde bei primär fortgeschrittenen Rektumkarzinomen nach präoperativer Radiochemotherapie und regionaler Hyperthermie geprüft und mit der histopathologisch ermittelten Tumorremission nach präoperativer Behandlung verglichen.nn Patienten und Methode: 35 Patienten mit primären Rektumkarzinomen (uT3/uT4) wurden MR-tomographisch mittels Oberflächenspule 4–6 Wochen nach Radiochemotherapie (n = 35) plus Hyperthermie (n = 23) vor der kurativen Resektion untersucht. Als Goldstandard für die Remission wurde der Vergleich von prätherapeutischer Endosonographie mit dem histopathologischen Befund des Resektats definiert.nn Ergebnisse: Das T-Studium nach präoperativer Behandlung wurde nur bei 19 von 35 Patienten (54%) korrekt wiedergegeben, bei neun von 20 Respondern überbenimmt und bei sieben von 15 Nonrespondern unterschätzt. Daneben wurde auch cie N-Kategorie bei 19 von 35 Patienten (54%) korrekt bestimmt (bei zwölf Respondern und sieben Nonrespondern). Eine Überschätzung trat bei vier Respondern und zwei Nonrespondern auf, eine Unterschätzung bei vier Respondern und sechs Nonrespondern.nn Schlussfolgerungen: Die MR-Bildgebung erwies sich trotz optimierter Aufnahmetechnik mit erhöhter räumlicher Auflösung und unabhängig vom Remissionsstatus als ungeeignet, das Stadium lokal fortgeschrittener Rektumkarzinome nach präoperativer Radiochemotherapie exakt zu ermitteln. Grundsätzlich ist die Darstellung der Morphologie eines Tumors nicht geeignet, zwischen vitalem und devitalisiertem Tumorgewebe nach Vorbehandlung zu differenzieren. Funktionelle Verfahren (z. B. die Positronenemissionstomographie) könnten für die Verlaufskontrolle nach Radiochemothermotherapie geeigneter sein.

Myopathy causing camptocormia in idiopathic Parkinson's disease: a multidisciplinary approach.

Extreme forward flexion of the spine, named camptocormia (CC), and head drop syndrome (HD) may be among the most disabling symptoms in Parkinsons disease (PD). This study aims to eludicate the etiology of PD‐associated CC and HD via a multidisciplinary approach (clinical examination, electromyography, MRI, genetic analysis, muscle morphology) centering on the histology of the paraspinal muscles. We studied 17 patients with the clinical diagnosis of PD and CC or head drop syndrome and six controls. We performed muscle biopsies of paraspinal muscles and deep neck extensor muscles. Mean age at onset of postural abnormality was 66 years and mean latency between onset of parkinsonian symptoms to first signs of CC or head drop was 7 years. The electromyogram of paraspinal muscles was abnormal in 13–14 patients. Histopathology revealed chronic myopathic changes in 14 of 17 biopsies, consisting of abnormal variation in fiber size, increase in internal nuclei, and increase in connective tissue, myofibrillar disarray and similarities to protein surplus myopathies. Interestingly, heterozygous variants in the Parkin gene were found in 2 of 9 investigated patients. We conclude that CC and HD in PD are predominantly myopathic. Aberrant protein aggregation may link PD and CC.

Gamma activity and reactivity in human thalamic local field potentials

Depth recordings in patients with Parkinson’s disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of ∼70u2003Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at ∼70u2003Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep–wake cycle, being suppressed during slow wave sleep and re‐emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle‐eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at ∼70u2003Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at ∼70u2003Hz may be involved in movement and arousal.

The human hippocampal formation mediates short-term memory of colour–location associations

The medial temporal lobe (MTL) has long been considered essential for declarative long-term memory, whereas the fronto-parietal cortex is generally seen as the anatomical substrate of short-term memory. This traditional dichotomy is questioned by recent studies suggesting a possible role of the MTL for short-term memory. In addition, there is no consensus on a possible specialization of MTL sub-regions for memory of associative information. Here, we investigated short-term memory for single features and feature associations in three humans with post-surgical lesions affecting the right hippocampal formation and in 10 healthy controls. We used three delayed-match-to-sample tasks with two delays (900/5000 ms) and three set sizes (2/4/6 items). Subjects were instructed to remember either colours, locations or colour-location associations. In colour-only and location-only conditions, performance of patients did not differ from controls. By contrast, a significant group difference was found in the association condition at 5000 ms delay. This difference was largely independent of set size, thus suggesting that it cannot be explained by the increased complexity of the association condition. These findings show that the hippocampal formation plays a significant role for short-term memory of simple visuo-spatial associations, and suggest a specialization of MTL sub-regions for associative memory.

Automated Optimization of Subcortical Cerebral MR Imaging−Atlas Coregistration for Improved Postoperative Electrode Localization in Deep Brain Stimulation

BACKGROUND AND PURPOSE: The efficacy of deep brain stimulation in treating movement disorders depends critically on electrode localization, which is conventionally described by using coordinates relative to the midcommissural point. This approach requires manual measurement and lacks spatial normalization of anatomic variances. Normalization is based on intersubject spatial alignment (coregistration) of corresponding brain structures by using different geometric transformations. Here, we have devised and evaluated a scheme for automated subcortical optimization of coregistration (ASOC), which maximizes patient-to-atlas normalization accuracy of postoperative structural MR imaging into the standard Montreal Neurologic Institute (MNI) space for the basal ganglia. MATERIALS AND METHODS: Postoperative T2-weighted MR imaging data from 39 patients with Parkinson disease and 32 patients with dystonia were globally normalized, representing the standard registration (control). The global transformations were regionally refined by 2 successive linear registration stages (RSs) (ASOC-1 and 2), focusing progressively on the basal ganglia with 2 anatomically selective brain masks, which specify the reference volume (weighted cost function). Accuracy of the RSs was quantified by spatial dispersion of 16 anatomic landmarks and their root-mean-square errors (RMSEs) with respect to predefined MNI-based reference points. The effects of CSF volume, age, and sex on RMSEs were calculated. RESULTS: Mean RMSEs differed significantly (P < .001) between the global control (4.2 ± 2.0 mm), ASOC-1 (1.92 ± 1.02 mm), and ASOC-2 (1.29 ± 0.78 mm). CONCLUSIONS: The present method improves the registration accuracy of postoperative structural MR imaging data into MNI space within the basal ganglia, allowing automated normalization with increased precision at stereotactic targets, and enables lead-contact localization in MNI coordinates for quantitative group analysis.

Reorganization of associative memory in humans with long-standing hippocampal damage

Conflicting theories have been advanced to explain why hippocampal lesions affect distinct memory domains and spare others. Recent findings in monkeys suggest that lesion-induced plasticity may contribute to the seeming preservation of some of these domains. We tested this hypothesis by investigating visuo-spatial associative memory in two patient groups with similar surgical lesions to the right medial temporal lobe, but different preoperative disease courses (benign brain tumours, mean: 1.8 +/- 0.6 years, n = 5, age: 28.2 +/- 4.0 years; hippocampal sclerosis, mean: 16.8 +/- 1.9 years, n = 9, age: 38.9 +/- 4.1 years). Compared to controls (n = 14), tumour patients showed a significant delay-dependent deficit in memory of colour-location associations. No such deficit was observed in hippocampal sclerosis patients, which appeared to benefit from a compensatory mechanism that was inefficient in tumour patients. These results indicate that long-standing hippocampal damage can yield significant functional reorganization of the neural substrate underlying memory in the human brain. We suppose that this process accounts for some of the discrepancies between results from previous lesion studies of the human medial temporal lobe.

Decreased bilateral cortical representation patterns in writer's cramp: a functional magnetic resonance imaging study at 3.0 T.

Functional magnetic resonance imaging was used to characterize patterns of cortical activation in response to sensory and motor tasks in patients with writer’s cramp. 17 patients and 17 healthy subjects were examined during finger-tapping, index finger flexion, and electrical median nerve stimulation of both hands during electromyographic monitoring. SPM2 was used to evaluate Brodmann area (BA) 4, 1, 2, 3, 6, 40. Patients showed decreased activation in the left BA 4 with motor tasks of both hands and the left BA 1–3 with right finger-tapping. With left finger-tapping there was bilateral underactivation of single areas of the somatosensory cortex. Patients exhibited decreased activation in the bilateral BA 6 with left motor tasks and in the right BA 6 with right finger-tapping. Patients had decreased activation in bilateral BA 40 with finger-tapping of both hands. The findings suggest decreased baseline activity or an impaired activation in response to motor tasks in BA 1–4, 6, 40 in patients with writer’s cramp for the dystonic and the clinically unaffected hand.

Diffusion tensor imaging in idiopathic Parkinson's disease and multisystem atrophy (Parkinsonian type).

Background: Differentiation between Parkinsons disease (PD) and atypical Parkinson syndromes (AP) is usually based on clinical examination, but can be challenging especially at early stages of the diseases. Diffusion tensor imaging (DTI) allows for differentiation between PD and AP with good specificity. It is a promising tool for clinical application, but has not been elaborated completely with respect to methodology and validity. Objective: In this study we evaluated differences of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within white brain matter between patients with PD and multisystem atrophy of the parkinsonian type (MSAp). Materials and Methods: DTI data of 9 PD and 9 MSAp patients were compared by means of a hypothesis-free whole-brain analysis algorithm (TBSS) focusing on changes within white matter. Results: We found significantly higher values of the ADC in the MSAp group in the anterior limb of the inner capsule, superior parts of the corona radiata, and lateral periputaminal white matter. Group differences in FA values were not significant. Conclusion: Changes of the ADC close to the putamen proved most consistent and seem to be promising for the ongoing clinical implementation of DTI for the differentiation of hypokinetic-rigid movement disorders.

Postoperative MRI localisation of electrodes and clinical efficacy of pallidal deep brain stimulation in cervical dystonia

Introduction Pallidal deep brain stimulation (DBS) has been shown to be effective in cervical dystonia (CD) with an improvement of about 50–60% in the Toronto Western Spasmodic Torticollis Rating (TWSTR) Scale. However, predictive factors for the efficacy of DBS in CD are missing with the anatomical location of the electrodes being one of the most important potential predictive factors. Methods In the present blinded observational study we correlated the anatomical localisation of DBS contacts with the relative clinical improvement (CI %) in the TWSTR as achieved by DBS at different pallidal contacts in 20 patients with CD. Localisations of DBS contacts were derived from postoperative MRI-data following anatomical normalisation into the standard Montreal Neurological Institute stereotactic space. The CIs following 76 bilateral test stimulations of 24u2005h were mapped to stereotactic coordinates of the corresponding bilateral 152 active contacts and were allocated to low CI (<30%; n=74), intermediate CI (≥30%; <60%; n=52) or high CI (≥60%; n=26). Results Euclidean distances between contacts and the centroid differed between the three clusters (p<0.001) indicating different anatomical variances between clusters. The Euclidean distances between contacts and the centroid of the cluster with high CIs correlated with the individual level of CIs (r=−0.61; p<0.0001). This relationship was best fitted with an exponential regression curve (r2=0.41). Discussion Our data show that the clinical effect of pallidal DBS on CD displays an exponential decay over anatomical distance from an optimised target localisation within a subregion of the internal pallidum. The results will allow a comparison of future DBS studies with postoperative MRI by verifying optimised (for instance pallidal) targeting in DBS-treated patients.