Neurobiologische und behaviorale Marker der Verarbeitung stressbezogener und affektiv negativer Stimuli bei Multipler Sklerose und deren Zusammenhang mit dem Erkrankungsschweregrad

Psychologischer Stress kann den Schweregrad von Multipler Sklerose (MS) beeinflussen. Die peripher-physiologische Stresssystemaktivität ist bei PatientInnen mit MS (PmMS) verändert, was mit einer abweichenden Verarbeitung allgemeiner affektiver negativer Reize einhergehen kann. Wenig ist über die neurobiologischen Faktoren von Entspannung bei PmMS bzw. die Verarbeitung allgemeiner affektiver Reize und über den Zusammenhang zwischen neuronalen Stress-Mechanismen und Krankheitsparametern bekannt. In drei Experimenten untersuchten wir (i) Zusammenhänge von stressinduzierter neuronaler Aktivität und neurologischen Erkrankungsschwereparametern, (ii) neurobiologische Korrelate von Entspannung nach Stress und (iii) evaluierten, ob es Hinweise auf abweichende Verarbeitungen affektiv negativer Stimuli gibt. Methodik: Experiment I: Der Zusammenhang zwischen Stress und Hirnaktivität wurde bei 36 PmMS und 21 gesunde KontrollprobandInnen (GK) mittels eines stresserzeugenden funktionellen Magnetresonanztomographie(fMRT)-Paradigmas untersucht, in dem Kopfrechenaufgaben gelöst und die Leistung bewertet wurde. Die erfassten fMRT-Signale korrelierten wir mit Krankheitsparametern. Experiment II: Innerhalb desselben Paradigmas erfassten wir psychologische Stress- und Entspannungsreaktionen durch Selbstbeurteilungsdaten. Als eine physiologische Stress-Reaktion wurde die Herzfrequenz (HF) gemessen. Das regionale Graue Substanz (GS)-Volumen wurde für die Untersuchung von neurobiologischen Korrelaten von Entspannung nach Stress bei MS über das gesamte Gehirn zu psychologischer Entspannung in Beziehung gesetzt. Experiment III: Zur affektiven Stimulusverarbeitungstestung (als Teilaspekt der belohnungsbezogenen Entscheidungsfindung) bei MS, nutzten wir eine fMRT-Version der Iowa-Gambling-Task (IGT). ProbandInnen sollten lernen, durch das Identifizieren und Auswählen gewinnbringender und das Vermeiden verlustbehafteter (affektiv positiv/negativ besetzter) Kartenstapel möglichst viel Gewinn zu erspielen. Wir untersuchten die zugrunde liegende neuronale Aktivität in den Entscheidungsfindungsprozessphasen. Ergebnisse: Experiment I: Neuronale Stressantworten im insulären Cortex korrelierten bei PmMS mit pyramidaler und cerebraler Funktionsbeeinträchtigung. Die cerebelläre Aktivität korrelierte negativ mit GS-Atrophie in beiden Gruppen. Experiment II: Anders als bei GK, war die Entspannungsbeurteilung innerhalb von PmMS signifikant schwächer an den HF-Rückgang und das ventromediale-präfrontale-Cortex (VMPFC)-Volumen gekoppelt. Experiment III: Schwerer betroffene PmMS zeigten im Vergleich mit GK einen weniger stark ausgeprägten Lerneffekt und erzielten weniger Gewinne bei höheren Verlusten. Die VMPFC-Aktivität spiegelte die Performanz über Personen beider Gruppen wider. Fazit: Stressinduzierte neuronale Aktivität spiegelt den Erkrankungsschweregrad wider und war mit GS-Volumenverlust in deckungsgleichen Arealen bei PmMS und GK assoziiert. Dies suggeriert, dass die Assoziation innerhalb von PmMS keinem ausschließlich reaktiven Mechanismus folgen kann. PmMS scheinen den Rückgang peripherer Stresssignale weniger gut in die Entspannungswahrnehmung integrieren zu können, was an Veränderungen in der Reizverarbeitung in zentralen Belohnungsarealen des Gehirns (VMPFC) gekoppelt zu sein scheint. Die Leistung in Aufgaben, die das Erlernen affektiver Reizeigenschaften erfordern, scheint bei PmMS reduziert. Das legt Verarbeitungsdefizit belohnungs- bzw. bestrafungsrelevanter Prozesse bei MS nahe.Psychological stress can influence the severity of Multiple Sclerosis (MS). Peripheral stress system activity alters in patients with MS (PwMS) compared to healthy controls (HC). This can be paired with an impaired processing of negative affective stimuli. Little is known about the underlying neurobiological factors of relaxation, the processing of affective stimuli and the association of neural stress-mechanisms and disease parameters in PwMS. We aimed to (i) investigate associations of stress-induced neural activity and neurological disease parameters, (ii) test neurobiological correlates of relaxation after stress-exposure and (iii) evaluate if the processing of negative affective stimuli in PwMS is impaired. Methods: Experiment I: We investigated the connection between stress and brain activity in 36 PwMS and 21 HC by using a stress-inducing arithmetical fMRI paradigm and correlated results with disease parameters. Experiment II: Psychological stress- and relaxation-responses were conducted by self- assessment in the same paradigm. Heart rate (HR) was determined as physiological stress response. We investigated regional gray-matter (GM)-volume throughout the brain as central nervous correlate of relaxation after stress exposure. Experiment III: To investigate the processing of affective stimuli (as part of reward-related decision making) in PwMS we used an fMRI-version of the Iowa-Gambling-Task (IGT). Subjects should learn to distinguish between reward- and loss-related card decks to win as much money as possible. We investigated the underlying brain-activity during different stages of decision making. Results: Experiment I: Neural stress-responses in the insular cortex correlated with pyramidal and cerebral impairment in PwMS. Cerebellar activity showed a negative association with GM- atrophy in both groups. Experiment II: In PwMS relaxation-perception showed a significantly lower association with a decline in HR and ventromedial-prefrontal-cortex (VMPFC)-volume compared to HC. Experiment III: VMPFC-activity during IGT correlated positively with performance in all subjects, with more severely affected PwMS showing a worse learning effect resulting in winning less money than HC. Conclusion: Stress-induced neural activity depicts disease-severity and was associated with GM-volume-loss in overlapping areas in both groups. This suggests that this association can not be caused by MS alone. It looks like PwMS were not able to integrate the decline of peripherical stress-signals in their perception of relaxation, which seems to be related to alterations in stimuli-processing in central reward-areas of the brain (VMPFC). The relevance of reward (or punishment)-related stimuli-processing in PwMS is supported by the correlation of performance in reward-related tasks and the activity in reward-related brain-areas (VMPFC) by simultaneously showing a worse IGT-performance compared to HC

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin's Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs

Quantitative Multiparametric Ultrasound (mpUS) in the Assessment of Inconclusive Cervical Lymph Nodes

Background: Enlarged cervical lymph nodes (CLN) are preferably examined by ultrasound (US) by using criteria such as size and echogenicity to assess benign and suspicious CLN, which should be histologically evaluated. This study aims to assess the differentiation of malign and benign CLN by using multiparametric US applications (mpUS). Methods: 101 patients received a standardized US protocol prior to surgical intervention using B-mode–US, shear-wave elastography (SWE) and contrast-enhanced ultrasound (CEUS). SWE was assessed by 2D real-time SWE conducting a minimum of five measurements, CEUS parameters were assessed with post-processing perfusion software. Histopathological confirmation served as the gold standard. Results: B-mode–US and SWE analysis of 104 CLN (36 benign, 68 malignant) showed a significant difference between benign and malignant lesions, presenting a larger long axis and higher tissue stiffness (both p < 0.001). Moreover, tissue stiffness assessed by SWE was significantly higher in CLN with regular B-mode–US criteria (Solbiati Index > 2 and short-axis < 1 cm, p < 0.001). No perfusion parameter on CEUS showed a significant differentiation between benign and malignant CLN. Discussion: As the only multiparametric parameter, SWE showed higher tissue stiffness in malignant CLN, also in subgroups with regular B-mode criteria. This fast and easy application may be a promising noninvasive tool to US examination to ameliorate the sonographic differentiation of inconclusive CLN

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin’s Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin’s Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs