Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation

Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus

Voraussetzungen für die Quantifizierung in der Emissions-Tomographie

Die Quantifizierung bei nuklearmedizinischen Untersuchungen bedeutet die Ermittlung der Aktivitätskonzentration im Gewebe und gegebenenfalls in einem weiteren Schritt die Bestimmung parametrischer Größen zur physiologischen Quantifizierung. Unter der Voraussetzung der korrekten Funktion des Gerätes (Qualitätskontrolle, Normalisierung, Kalibrierung) ist für die Quantifizierung die Anwendung folgender Korrekturen notwendig: Totzeit-, Absorptions-, Streustrahlungs- und ggf. Recovery-Korrektur wie auch Korrektur von zufälligen Koinzidenzen. Aus messtechnischer Sicht basiert die Überlegenheit der PET gegenüber der SPECT auf den Vorteilen des Einsatzes des Koinzidenznachweises (elektronische Kollimierung) anstelle der mechanischen Kollimierung in entsprechend konstruierten ringförmigen Systemen, welche sich in überlegenen physikalischen Abbildungseigenschaften niederschlägt. Der primäre Vorteil der elektronischen Kollimierung ist eine bessere und mehr stationäre räumliche Auflösung, gepaart mit einer höheren Meßempfindlichkeit, welche zu statistisch aussagefähigerer Bildqualität führt, und die Möglichkeit einer geradlinigen, aber präzisen Form der Absorptionskorrektur auf der Basis gemessener Transmissionsdaten. Weitere Vorteile sind ein deutlich verringerter Streustrahlungsanteil, welcher in Verbindung mit den vorstehend genannten Eigenschaften zu kontrast- und detailreicheren Bildern führt, sowie eine deutliche Steigerung der Zählratenkapazität, die durch eine Steigerung der Anzahl der voneinander unabhängigen Zählkanäle bei Verwendung der üblichen Blockdetektoren erreicht wird und die es erlaubt, die gesteigerte Ausbeute ohne einen Zwang zur Aktivitätsreduktion in statistische Bildqualität umzusetzen. Die dargestellten Eigenschaften gestatten dann in Verbindung mit gut entwickelten Korrekturverfahren eine Kalibrierung des PET-Systems und damit die quantitative Analyse von in vivo gemessenen Aktivitätskonzentrationen. Berücksichtigt man die Problematik der Absorptions- und Streustrahlungskorrektur bei der SPECT, so ergibt sich als Folgerung, dass bei der Tomographie mit der Gammakamera eine Quantifizierung nicht möglich ist. Aufgrund der Entwicklungen auf dem Gebiet der Rekonstruktions- und Korrekturverfahren kann damit gerechnet werden, dass die Abbildungseigenschaften von SPECT-Systemen verbessert werden, so dass viele Limitationen der SPECT-Technik zumindest abgemildert werden dürften, die Leistung der PET-Geräte aus physikalischen Gründen jedoch nicht erreicht werden kann.Quantifying in nuclear medicine examinations is equivalent to the determination of local activity concentrations in human tissue and, if appropriate, in an additional step the determination of quantitative physiological parameters. Provided that the instrument is in proper working conditions (quality control, normalization, calibration) quantification requires the application of the following corrections for: dead time, attenuation, scatter and, if applicable, recovery as well as random coincidences. From the physical point of view the superiority of PET over SPECT is based on the advantages offered by coincidence detection (electronic collimation) as compared to mechanical collimation. For ring-type systems of the appropriate design these advantages result in superior imaging quality. The main advantage of the aforementioned electronic collimation is given by a better and more stationary spatial resolution, accompanied by a higher sensitivity resulting in an improved statistical image quality, and an attenuation correction method based on measured transmission data, which is straightforward and accurate. Further advantages are a markedly reduced scatter fraction, leading in combination with the aforementioned properties to images of high contrast and high detail, and a pronounced improvement in count rate performance, caused by an increased number of independent counting channels when using state-of-the-art block detectors. This higher count rate performance allows to transform increased sensitivity without being obliged to reduce administered activity into improved statistical image quality. In conjunction with well established correction methods the physical properties of PET described allow for a calibration of the system and, therefore, for a quantitative analysis of activity concentrations in vivo. Realizing the problems associated with attenuation and scatter correction in gamma camera based tomography leads to the conclusion that quantification in SPECT is not feasible. Taking into account further progress in reconstruction algorithms and correction methods, improvements in SPECT imaging quality may be anticipated thereby diminishing current limitations of the SPECT technique. Nevertheless, by physical arguments the performance of PET cannot be achieved

Visualization of the auditory pathway in rats with 18F-FDG PET activation studies based on different auditory stimuli and reference conditions including cochlea ablation.

Activation studies with positron emission tomography (PET) in auditory implant users explained some of the mechanisms underlying the variability of achieved speech comprehension. Since future developments of auditory implants will include studies in rodents, we aimed to inversely translate functional PET imaging to rats. In normal hearing rats, activity in auditory and non-auditory regions was studied using 18F-fluorodeoxyglucose (18F-FDG) PET with 3 different acoustic conditions: sound attenuated laboratory background, continuous white noise and rippled noise. Additionally, bilateral cochlea ablated animals were scanned. 3D image data were transferred into a stereotaxic standard space and evaluated using volume of interest (VOI) analyses and statistical parametric mapping (SPM). In normal hearing rats alongside the auditory pathway consistent activations of the nucleus cochlearis (NC), olivary complex (OC) and inferior colliculus (IC) were seen comparing stimuli with background. In this respect, no increased activation could be detected in the auditory cortex (AC), which even showed deactivation with white noise stimulation. Nevertheless, higher activity in the AC in normal hearing rats was observed for all 3 auditory conditions against the cochlea ablated status. Vice versa, in ablated status activity in the olfactory nucleus (ON) was higher compared to all auditory conditions in normal hearing rats. Our results indicate that activations can be demonstrated in normal hearing animals based on 18F-FDG PET in nuclei along the central auditory pathway with different types of noise stimuli. However, in the AC missing activation with respect to the background advises the need for more rigorous background noise attenuation for non-invasive reference conditions. Finally, our data suggest cross-modal activation of the olfactory system following cochlea ablation-underlining, that 18F-FDG PET appears to be well suited to study plasticity in rat models for cochlear implantation

Radiotherapy of Breast Cancer in Laterally Tilted Prone vs. Supine Position: What about the Internal Mammary Chain?

Background: In the multimodal breast-conserving curative therapy of some high-risk breast cancer patients, extended external beam radiotherapy (EBRT) not only to the breast but also to the supraclavicular fossa and the internal mammary chain (parasternal region (PSR)) is indicated. We report a dosimetric study on the EBRT of the breast (“B”) and the breast including PSR (“B + PSR”), comparing the supine and the laterally tilted prone patient positions in free breathing. Methods: The planning CT scans of 20 left- and 20 right-sided patients were analyzed. EBRT plans were calculated with 3D conformal EBRT (3D) and with intensity-modulated EBRT (IMRT) for “B” and “B + PSR” in the prone and supine positions. The mean and threshold doses were computed. The quality of EBRT plans was compared with an overall plan assessment factor (OPAF), comprising three subfactors, homogeneity, conformity, and radiogenic exposure of OAR. Results: In the EBRT of “B”, prone positioning significantly reduced the exposure of the OARs “heart” and “ipsilateral lung” and “lymphatic regions”. The OPAF was significantly better in the prone position, regardless of the planning technique or the treated breast side. In the EBRT of “B + PSR”, supine positioning significantly reduced the OAR “heart” exposure but increased the dose to the OARs “ipsilateral lung” and “lymphatic regions”. There were no significant differences for the OPAF, independent of the irradiated breast side. Only the IMRT planning technique increased the chance of a comparatively good EBRT plan. Conclusion: Free breathing prone positioning significantly improves plan quality in the EBRT of the breast but not in the EBRT of the breast + PSR

Combined Brain-Perfusion SPECT and EEG Measurements Suggest Distinct Strategies for Speech Comprehension in CI Users With Higher and Lower Performance

Cochlear implantation constitutes a successful therapy of inner ear deafness, with the majority of patients showing good outcomes. There is, however, still some unexplained variability in outcomes with a number of cochlear-implant (CI) users, showing major limitations in speech comprehension. The current study used a multimodal diagnostic approach combining single-photon emission computed tomography (SPECT) and electroencephalography (EEG) to examine the mechanisms underlying speech processing in postlingually deafened CI users (N= 21). In one session, the participants performed a speech discrimination task, during which a 96-channel EEG was recorded and the perfusions marker(99m)Tc-HMPAO was injected intravenously. The SPECT scan was acquired 1.5 h after injection to measure the cortical activity during the speech task. The second session included a SPECT scan after injection without stimulation at rest. Analysis of EEG and SPECT data showed N400 and P600 event-related potentials (ERPs) particularly evoked by semantic violations in the sentences, and enhanced perfusion in a temporo-frontal network during task compared to rest, involving the auditory cortex bilaterally and Broca's area. Moreover, higher performance in testing for word recognition and verbal intelligence strongly correlated to the activation in this network during the speech task. However, comparing CI users with lower and higher speech intelligibility [median split with cutoff + 7.6 dB signal-to-noise ratio (SNR) in the Gottinger sentence test] revealed for CI users with higher performance additional activations of parietal and occipital regions and for those with lower performance stronger activation of superior frontal areas. Furthermore, SPECT activity was tightly coupled with EEG and cognitive abilities, as indicated by correlations between (1) cortical activation and the amplitudes in EEG, N400 (temporal and occipital areas)/P600 (parietal and occipital areas) and (2) between cortical activation in left-sided temporal and bilateral occipital/parietal areas and working memory capacity. These results suggest the recruitment of a temporo-frontal network in CI users during speech processing and a close connection between ERP effects and cortical activation in CI users. The observed differences in speech-evoked cortical activation patterns for CI users with higher and lower speech intelligibility suggest distinct processing strategies during speech rehabilitation with CI

Expert System for Bone Scan Interpretation Improves Progression Assessment in Bone Metastatic Prostate Cancer.

INTRODUCTION The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIbone(BSI) seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA). METHODS In 49 mPCa patients, bone scans were performed initially and during different therapy courses. Scans were evaluated visually and by the artificial-neural-network-based expert system EXINIbone(BSI). Progression of metastatic bone involvement was defined according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria in the visual interpretation. The computer-assisted interpretation was based on different cutoff values in relative changes of the aBSI. Additionally, assessments according to bone scanning were compared to changes in the PSA value as a potential surrogate for treatment response. RESULTS Using a sensitive cutoff value (5% or 10%) for the relative aBSI increase led to significantly increased progression determination compared to the visual interpretation of bone scans (49% and 43% vs. 27%, p < 0.001). In 63% of the cases PSA and BSI changes matched, whereas in 18% progression was only indicated by the aBSI. A relative cutoff of 5% for the aBSI decrease could reclassify 47 serial scan pairs which were visually interpreted as stable into 22 progressive and 25 remissive scans. CONCLUSION Distinct thresholds of the relative aBSI could help to better assess disease progression in mPCa patients. Manual corrections of the BSI values are not required in most cases. The aBSI could serve as a useful additional parameter for therapy monitoring in mPCa patients in the future