Multidisciplinary Postoperative Validation of 18F-FDG PET/CT Scan in Nodal Staging of Resected Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to examine the validity of PET/CT scans in the preoperative identification of lymph node metastases (LNM) and compare them with postoperative outcomes. METHODS: In this retrospective study, we included 87 patients with a solitary lung nodule or biopsy-proven non-small cell lung cancer treated in our institution from 2009 to 2015. Patients were divided into two groups and four subgroups, depending on pre- and postoperative findings. RESULTS: According to our analysis, PET/CT scan has a sensitivity of 50%, a specificity of 88.89%, a positive predictive value of 63.16%, and a negative predictive value of 82.35%. Among the patients, 13.8% were downstaged in PET-CT, while 8% were upstaged. In 78.2% of cases, the PET/CT evaluation was consistent with the histology. Metastases without extracapsular invasion were seldom recognized on PET/CT. CONCLUSIONS: This analysis showed the significance of extracapsular tumor invasion, which causes an inflammatory reaction, on LNM, which is probably responsible for preoperative false-positive findings. In conclusion, PET/CT scans are very effective in identifying patients without tumors. Furthermore, it is highly probable that patients with negative findings are free of disease.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries.

BACKGROUND: The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. METHODS: Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (pathological FDG uptake) or follow-up examinations (non-pathological FDG uptake). The endpoints for comparison with the FDG uptake were either histological results or sonographic follow-up examinations of at least five years. RESULTS: In 18/65 (28%) patients, PET/CT showed visually pathological FDG uptake in the suspicious thyroid nodules (SUVmax 7.1 ± 4.6). Of these nodules, 3/18 (17%) were sonographically categorized as TIRADS 4a, 11/18 (61%) nodules as TIRADS 4b, 3/18 (17%) nodules as TIRADS 4c, and 1/18 (6%) nodule as TIRADS 5. The other nodules without pathological FDG uptake were categorized as TIRADS 4a in 24/47 (51%) patients, as TIRADS 4b in 18/47 (38%), and as TIRADS 4c in 5/47 (11%) patients. Twenty-three patients (18 FDG positive, 5 FDG negative) underwent surgery. The other patients underwent follow-up examinations with stability on observation over at least five years as a surrogate endpoint. Taking into consideration that FDG-PET/CT was rated as true negative in 42/47 patients with stability on sonographic follow-up, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT in detecting malignancy in the suspicious thyroid nodules were 100%, 87%, 61%, and 100%, respectively. CONCLUSION: FDG-PET/CT allows stratification of patients with sonographically suspicious and scintigraphically hypofunctional thyroid nodules with a positive predictive value of 61% and negative predictive value of 100%. The absence of visually pathological FDG uptake in suspicious thyroid nodules may be useful for avoiding unnecessary thyroid surgery.

Callosal tissue loss in multiple system atrophy--a one-year follow-up study.

Multiple system atrophy (MSA) is a neurodegenerative disease not only affecting the basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord but also the cerebral cortex. Clinically, cerebellar (MSA-C) and parkinsonian variants of MSA (MSA-P) are distinguished. We investigated 14 MSA patients (10 MSA-C, 4 MSA-P, men: 7, women: 7; age: 61.1 ± 3.3 years) and 14 matched controls (men: 7, women: 7; age: 58.6 ± 5.1 years) with voxel-based morphometry (VBM) to analyze gray and white matter differences both at baseline and at follow-up, 1 year later. Baseline comparisons between patients and controls confirmed significantly less gray matter in MSA in the cerebellum and cerebral cortex, and significantly less white matter in the cerebellar peduncles and brainstem. Comparisons of tissue-loss profiles (i.e., baseline versus follow-up) between patients and controls, revealed white matter reduction in MSA along the middle cerebellar peduncles, reflecting degeneration of the ponto-cerebellar tract as a particularly prominent and progressive morphological alteration in MSA. Comparisons between baseline and follow-up, separately performed in patients and controls, revealed additional white matter reduction in MSA along the corpus callosum at follow-up. This was replicated through additional shape-based analyses indicating a reduced callosal thickness in the anterior and posterior midbody, extending posteriorly into the isthmus. Callosal atrophy may possibly reflect a disease-specific pattern of neurodegeneration and cortical atrophy, fitting well with the predominant impairment of motor functions in the MSA patients.

In vivo voxel-based relaxometry in amyotrophic lateral sclerosis.

We applied voxel-based relaxometry (VBR) in 12 ALS patients and 12 matched healthy controls and compared the results with those of voxel-based morphometry (VBM). VBR revealed a reduced relaxation rate in the right precentral gyrus and ventral pons. Individual region of interest (ROI)-based analysis of R2 maps confirmed our VBR results. VBM depicted a reduction of white matter in the paracentral lobules and in the right middle cerebellar peduncle. Our data suggests that VBR and ROI analysis of R2 maps may have a higher sensitivity in detecting local tissue atrophy in the motor cortex and along the corticospinal tract than VBM. Larger prospective studies are necessary to evaluate the usefulness and relevance of VBR and ROI-based analysis of R2 maps in clinical practice.

Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2.

Myotonic dystrophy type 2 (DM2) is an autosomal dominantly inherited multisystemic disorder and a common cause of muscular dystrophy in adults. Although neuromuscular symptoms predominate, there is clinical and imaging evidence of cerebral involvement. We used voxel-based morphometry (VBM) based on T1-weighted magnetic resonance images to investigate brain morphology in 13 DM2 patients in comparison to 13 sex- and age-matched controls. Further, we employed novel computational surface-based methods that specifically assess callosal thickness. We found grey and white matter loss along cerebral midline structures in our patient group. Grey matter reductions were present in brainstem and adjacent hypothalamic and thalamic regions, while white matter was mainly reduced in corpus callosum. The reduced callosal size was highly significant and independently confirmed by different methods. Our data provide first evidence for grey and white matter loss along brain midline structures in DM2 patients. The reduced size of the corpus callosum further extends the spectrum of white matter changes in DM2 and may represent the morphological substrate of neuropsychological abnormalities previously described in this disorder.

Functional dissociations in top-down control dependent neural repetition priming.

Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either pictures or words that were presented superimposed on each other. In the repetition phase only words were presented that were new, previously attended or ignored, or picture names that were derived from previously attended or ignored pictures. Relative to new words we found repetition priming for previously attended words. Previously ignored words showed a reduced priming effect, and there was no significant priming for pictures repeated as picture names. Brain imaging data showed that neural priming of words in the left prefrontal cortex (LIPFC) and left fusiform gyrus (LOTC) was affected by attention, semantic compatibility of superimposed stimuli during study and cross-modal priming. Neural priming reduced for words in the LIPFC and for words and pictures in the LOTC if stimuli were previously ignored. Previously ignored words that were semantically incompatible with a superimposed picture during study induce increased neural priming compared to semantically compatible ignored words (LIPFC) and decreased neural priming of previously attended pictures (LOTC). In summary, top-down control induces dissociable effects on neural priming by attention, cross-modal priming and semantic compatibility in a way that was not evident from behavioral results.

Presurgical language fMRI in patients with drug-resistant epilepsy: effects of task performance.

PURPOSE: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels. METHODS: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels. RESULTS: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation. CONCLUSIONS: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.

Association between scalp hair-whorl direction and hemispheric language dominance.

Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy.

It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the hippocampus has been challenged by recent studies. This study was undertaken to assess the effect of lesions in different parts of the left hemisphere, lesions present during language acquisition, on language lateralization. We investigated 84 adult patients with drug-resistant focal epilepsy with structural lesions and 45 healthy control subjects with an established functional MRI language paradigm. Out of the 84 patients 43 had left hippocampal sclerosis, 13 a left frontal lobe lesion and 28 a left temporal-lateral lesion. All these lesions were likely to have been present during the first years of life during language acquisition. To assess the lateralization of cerebral language representation globally as well as regionally, we calculated lateralization indices derived from activations in four regions of interest (i.e. global, inferior frontal, temporo-parietal and remaining prefrontal). Patients with left hippocampal sclerosis showed less left lateralized language representations than all other groups of subjects (P < 0.005). This effect was independent of the factor of region, indicating that language lateralization was generally affected by a left hippocampal sclerosis. Patients with left frontal lobe or temporal-lateral lesions displayed the same left lateralization of language-related activations as the control subjects. Thus, the hippocampus seems to play an important role in the establishment of language dominance. Possible underlying mechanisms are discussed.

Functional infrared imaging for skin-cancer screening.

Annually 133.000 people world-wide get sick on malign melanoma, tendency increasing. The purpose of this study is the early diagnosis of malignant skin cancer. At the moment the dermatologists are screening for anomalies at the relevant lesion by examining the skin area with a microscope. To determine changes, another scan has to be taken in a follow-up session after a time period of about 15-20 weeks. Today's visual diagnostic decision is based on the pragmatic ABCD approach (Asymmetry, Border, Colour, and Diameter). However, there is no adequate and sound non-invasive way to find out, if a skin spot is either malign or benign. If the visual approach corroborates a suspicion of skin cancer, histology is needed to make explicit diagnosis. To avoid unnecessary surgeries (on false positive alarm) and to initiate necessary surgeries in early stages a new diagnostic screening approach is presented here. Based on the fact that malign melanoma have higher metabolism as well as increased blood flow, it has been conjectured that malign melanoma have slightly higher temperature compared to the healthy skin that can be measured by high resolution functional infrared imaging.

Development of a radiation therapy open-source platform.

Although several industrial radio-therapy planning solutions presently exist, most of them do not cover the customer needs sufficiently. The aim of this project is to develop an open source radio-therapy planning system that would offer the ground work for individual customer solutions. During the first stage of the project we concentrate on the development of a visualisation module, since it is required for other parts such as dose calculation and beam modelling. The visualisation module will feature 2D and 3D visualisation of CT-, MRI- and PET DICOM images, registration of the images using Normalised Mutual Information, 2D and 3D visualisation of the matched images as well as 2D and 3D user interaction. In this paper an outline for our system is presented as well as a registration module, which is the first part of the visualisation module.

Process dissociation between contextual retrieval and item recognition.

We employed a source memory task in an event related fMRI study to dissociate MTL processes associated with either contextual retrieval or item recognition. To introduce context during study, stimuli (photographs of buildings and natural landscapes) were transformed into one of four single-color-scales: red, blue, yellow, or green. In the subsequent old/new recognition memory test, all stimuli were presented as gray scale photographs, and old-responses were followed by a four-alternative source judgment referring to the color in which the stimulus was presented during study. Our results suggest a clear-cut process dissociation within the human MTL. While an activity increase accompanies successful retrieval of contextual information, an activity decrease provides a familiarity signal that is sufficient for successful item recognition.

Using visual advance information: an event-related functional MRI study.

Our event-related functional MRI (efMRI) study investigates whether visual advance information (AI) affects rather perceptual or central response-related processing areas. Twelve subjects were required to make a go/no-go decision to a conjunction of a specific color and motion direction. The stimuli were preceded by a cue, providing 100% valid advance information about motion direction. Partial and full advance information (PAI and FAI) predicted possible targets, respectively, certain nontargets, neutral cues (NAI) gave no prediction. The time between cue and stimulus (stimulus onset asynchrony, SOA) was varied. A response benefit was found after PAI as compared with NAI. The benefit was small with a short SOA (150 ms), increased with intermediate SOA (450 ms) and sustained with long SOA (750 ms). Perceptual and central processing areas were more active with increasing SOA, but only central response-related processing areas were selectively modulated by cue information. In particular, supplementary motor area and bilateral inferior parietal lobe were more active with PAI than with NAI. If comparing NAI with FAI, more errors were made and activity was larger in central processing areas. Our results suggest that, depending on the processing time, cues providing perceptual information modulate central response-related processes.

Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.