Στην παρούσα μελέτη παρουσιάσαμε τα αποτελέσματα της λειτουργικής απεικόνισης με SPECT αιμάτωσης εγκεφάλου σε δύο διαφορετικές παθολογικές καταστάσεις, την νόσο του Παρκινσον και τη δευτεροπαθή δυστονία. Στο πρώτο μέρος της μελέτης διερευνήσαμε την ακεραιότητα της μελανοραβδωτής οδού και την αιματική εγκεφαλική ροή στα διάφορα στάδια της νόσου Parkinson. Στη μελέτη συμμετείχαν συνολικά 53 ασθενείς (27 άνδρες, 26 γυναίκες) που πληρούσαν τα κριτήρια της Ιδιοπαθούς νόσου του Parkinson και αξιολογήθηκαν σύμφωνα με την κλίμακα Unified Parkinson Disease Rating Scale (UPDRS) καθώς και την κλίμακα Hoehn-Yahr. Οι ασθενείς χωρίστηκαν σε 4 ομάδες σύμφωνα με την κλίμακα Hoehn-Yahr. Το πρωτόκολλο μελέτης των 53 ασθενών περιελάμβανε 2 απεικονιστικές εξετάσεις: Α) το SPECT εγκεφάλου με το ραδιοφάρμακο 123Ι- Ioflupane (DaTSCAN) και Β) το SPECT αιμάτωσης εγκεφάλου με το ραδιοφάρμακο 99m Tc-ECD (Neurolite ). Η νόσος Πάρκινσον είναι ένα υποκινητικό σύνδρομο και όπως καταδείξαμε από τη μέλετη ασθενών σε διάφορα στάδια της νόσου, το πρότυπο της αιμάτωσης του εγκεφάλου είναι αυτό της σταδιακής προσβολής περιοχών του φλοιού ως συνέπεια της απόσχισης των συνδέσεων του κυκλώματος βασικών γαγγλίων με το φλοιό. Συγκεκριμένα αποδείξαμε ότι στα αρχικά στάδια της νόσου παρατηρείται υποαιμάτωση περιοχών του μετωπιαίου λοβού (κινητικών, προκινητικών και περιοχών του προμετωπαίου λοβού) ενώ σε πιο προχωρημένα στάδια η προσβολή του φλοιού επεκτείνεται σε περιοχές του βρεγματικού και κροταφικού λοβού. Επίσης βρέθηκε θετική συσχέτιση μεταξύ της ειδικής σύνδεσης του ρ/φ στον αριστερό κερκοφόρο πυρήνα και της αιματικής εγκεφαλικής ροής στην περιοχή DLPFC του προμετωπιαίου λοβού αριστερά, καθώς επίσης και μεταξύ της ειδικής σύνδεσης του ρ/φ στο αριστερό κέλυφος και της αιματικής εγκεφαλικής ροής στην πρωτοταγή κινητική περιοχή αριστερά. Στο δεύτερο μέρος της εργασίας μελετήσαμε 21 ασθενείς με Ιδιοπαθή νόσο Parkinson που πληρούσαν τα κριτήρια για χειρουργική αντιμετώπιση με εν τω βάθει εγκεφαλικό ερεθισμό (DBS). Οι ασθενείς ήταν 11 γυναίκες και 10 άνδρες, μέσης ηλικίας 63±8 χρόνια, μέσης διάρκειας της νόσου 11.5±4.8 και σταδίου 2.9±0.8 κατά Hoehn and Yahr. Οι ασθενείς αυτοί υπεβλήθησαν σε 2 ξεχωριστές μελέτες SPECT αιμάτωσης εγκεφάλου, η πρώτη πριν το χειρουργείο (meds off) και η δεύτερη 6 μήνες μετά το χειρουργείο (DBS on/ off meds). Οι δύο αυτές μελέτες συγκρίθηκαν μεταξύ τους με το πρόγραμμα Neurogam και εξετάστηκαν συγκεκριμένα οι μεταβολές στην αιματική εγκεφαλική ροή των κινητικών περιοχών του εγκεφάλου. Παράλληλα εξετάσθηκε η κινητική βελτίωση των ασθενών κλινικά και με βάση την κλίμακα mUPDRS. Τα αποτελέσματα της μελέτης ήταν πολύ καλά καθώς οι 20 ασθενείς παρουσίασαν σημαντική κλινική βελτίωση μειώνοντας την κλίμακα mUPDRS κατά 44% και τη χορηγούμενη δόση levodopa από 850 ± 108 mg πριν το χειρουργείο σε 446 ± 188 mg στο διάστημα επανελέγχου. Επίσης στους 6 μήνες παρατηρήθηκε σημαντική αύξηση της αιματικής εγκεφαλικής ροής στην προκινητική και πρωτοταγή κινητική περιοχή του εγκεφαλικού φλοιού κατά 10.9% και σημαντική συσχέτιση αυτής με την κινητική βελτίωση των ασθενών (r=.89, p<.001). Από τη μελέτη μας προκύπτει ότι το DBS είναι ικανό να άρει την υποαιμάτωση τουλάχιστον των κινητικών περιοχών του φλοιού, οδηγώντας στην κινητική βελτίωση των ασθενών. Στο τρίτο μέρος της μελέτης μας ασχοληθήκαμε με την μελέτη ασθενών με δευτεροπαθή δυστονία που αποτελεί ένα υπερκινητικό σύνδρομο με ετερογένεια όσον αφορά την αιτιολογία του. Συγκεκριμένα μελετήσαμε το αποτέλεσμα της δράσης του DBS στην περιοχική αιματική εγκεφαλική ροή των κινητικών περιοχών του φλοιού σε συνάρτηση με το κλινικό αποτέλεσμα. Στο πρωτόκολλο πριελήφθησαν 6 ασθενείς με φαρμακευτικά ανθεκτική δευτεροπαθή δυστονία που υπεβλήθησαν σε DBS. Οι ασθενείς υπεβλήθησαν σε SPECT αιμάτωσης εγκεφάλου σε δύο διαφορετκές λειτουργικές καταστάσεις μετεγχειρητικά: DBS on & DBS off κατάσταση. Οι δύο μελέτες συγκρίθηκαν μεταξύ τους με το πρόγραμμα Neurogam. Η κινητική εκτίμηση των ασθενών έγινε με την κλίμακα Burke–Fahn–Mardsen Dystonia Rating Scale (BFMDRS) στις δυο διαφορετικές καταστάσεις (DBS on & DBS off). Δύο ασθενείς έδειξαν άριστη κλινική βελτίωση στον επανέλεγχο, σε δύο άλλους τα αποτελέσματα ήταν μέτρια και σε δύο τα αποτελέσματα της επέμβασης κρίθηκαν φτωχά. Ο μέσος βαθμός βελτίωσης της κλίμακας BFMDRS ήταν 49.1% (0–90.7%). Επίσης η ανάλυση των SPECT μελετών έδειξε σημαντική μείωση της rCBF στην κατάσταση on DBS κάτι που συσχετίστηκε με την κλινική βελτίωση. Όσον αφορά το μηχανισμό δράσης του εν τω βάθη εγκεφαλικού ερεθισμού, παρά τις πολλαπλές θεωρίες που υπάρχουν, φαίνεται, τουλάχιστον από το δικό μας μικρό δείγμα ασθενών, να λειτουργεί με το να επαναρυθμίζει το υπάρχων παθολογικό λειτουργικό κύκλωμα σε ένα νέο πιο αρμονικό ρυθμό, προσφέροντας στους ασθενείς μία νέα οδό επικοινωνίας του συστήματος των βασικών γαγγλίων με το φλοιό και στις περισσότερες περιπτώσεις να καταφέρνει να προσφέρει κινητική βελτίωση. / In the present study we present the results of functional brain imaging with regional Cerebral Blood Flow SPECT (rCBF SPECT) in two different neurological disorders; Parkinson’ Disease (PD) and Secondary Dystonia. In the first case of Parkinson’s Disease, our first purpose was to investigate the differences and associations between cortical perfusion and nigrostriatal dopamine pathway in different stages of Parkinson’s disease (PD). For that purpose we recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding). Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Compared with controls, PD patients showed impairments of cerebral perfusion that increased with clinical severity. Furthermore Dopamine transporter binding in the left caudate nucleus and putamen significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC) and primary motor cortex respectively. We concluded that there are significant perfusion deficits, that are associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc). Given the fact that high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an established therapeutic approach for the management of patients with medically intractable idiopathic Parkinson’s disease (PD), our second purpose was to to assess regional cerebral blood flow (rCBF) changes related to motor improvement after Deep Brain Stimulation of the Subthalamic Nucleus (STN DBS). For that purpose we studied twenty-one PD patients (11 females and 10 males, mean age 63±8, mean disease duration 11.5±4.8, mean Hoehn and Yahr stage:2.9±0.8), that underwent two rCBF SPECT studies at rest, once preoperatively in the off-meds state and the other postoperatively (at 6±2 months) in the off-meds/on-stimulation state. Patients were classified according to the Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. Neurogam software was used to register, quantify and compare two sequential brain SPECT studies of the same patient in order to investigate rCBF changes during STN stimulation in comparison with preoperative rCBF. The results showed that all patients presented clinical improvement during the first months after surgery resulting in a 44% reduction of the UPDRS motor score. The administered mean daily levodopa dose significantly decreased from 850 ± 108 mg before surgery to 446 ± 188 mg during off meds state (p < .001, paired t-test). At the 6 month postoperative assessment we noticed rCBF increases in the pre-supplementary motor area (pre-SMA) and the premotor cortex (PMC) (mean rCBF increase=10.9%), the dorsolateral prefrontal cortex and in associative and limbic territories of the frontal cortex (mean rCBF increase=8.2%). A correlation was detected between the improvement in motor scores and the rCBF increase in the pre-SMA and PMC (r=.89, p<.001). Our study suggests that STN stimulation leads to improvement in neural activity in the frontal motor/associative areas. The correlation between motor improvement and rCBF increase in higher order motor cortical areas suggests that even the short term stimulation achieves its therapeutic benefit by restoring the activity within these cortical regions. In the third part of our study we investigated the effect of deep brain stimulation (DBS) on regional cerebral blood flow (rCBF) in cases of secondary dystonia in correlation with clinical outcomes. For that purpose we studied six patients with medically intractable secondary dystonia who underwent DBS surgery. Burke–Fahn–Mardsen Dystonia Rating Scale (BFMDRS) was used for the assessment of dystonia, in the on & off DBS state. Single photon emission computed tomography (SPECT) of the brain was performed postoperatively in the two stimulation states (ON-DBS and OFFDBS) and the changes of rCBF in the three following brain regions of interest (ROIs): primary motor cortex, premotor and supplementary motor cortex, and prefrontal cortex were evaluated. Two patients exhibited excellent response to DBS, two patients got moderate benefit after the procedure, and in two patients, no clinical improvement was achieved. A mean improvement of 49.1% (0–90.7%) in BFMDRS total scores was found postoperatively. Brain SPECT data analysis revealed an overall decrease in rCBF in the investigated ROIs, during the ON-DBS state. Clinical improvement was significantly correlated with the observed decrease in rCBF in the presence of DBS. We concluded that when conservative treatment fails to relieve severely disabled patients suffering from secondary dystonia, DBS may be a promising therapeutic alternative. Moreover, thiat study indicates a putative role of brain SPECT imaging as a postoperative indicator of clinical responsiveness to DBS.

Bakgrund: Deep Brain Stimulation (DBS) i nucleus subthalamicus (STN) och i kaudala zona incerta (cZi) har visat positiva effekter på motoriska symtom (rörelseförmåga och balans) vid Parkinsons sjukdom. Efter DBS har dock negativa taleffekter noterats, inklusive nedsatt artikulatorisk precision och stabilitet. Nedsatt artikulatorisk precisionoch stabilitet påverkar klusilproduktionen mest vilket kan resultera i att klusilexplosionen uteblir eller att multipla explosioner uppstår. Mål: Att undersöka artikulatorisk precision och stabilitet vid klusilexplosionen efter DBS i STN respektive cZi. Metod: I studien deltog 19 patienter varav 9 deltagare stimulerats i STN och 10 deltagare i cZi. Talinspelningar gjordes innan operation och ett år efter operation med DBSstimulering på och av. Klusilerna i talmaterialet delades in i tre kategorier, de med en klusilexplosion, de med två eller flera klusilexplosioner samt de utan klusilexplosion. Hypotesprövning gjordes gällande fördelningen av klusiler med multipla explosioner samt klusiler utan explosion mellan och inom patientgrupperna samt inom respektive klusil. Resultat: Multipla explosioner ökade hos cZi-patienterna och minskade hos STNpatienterna. Klusiler som saknade explosion ökade hos STN-patienterna medan de minskade hos cZi-patienterna. För båda patientgrupperna ökade multipla explosioner och klusiler utan explosion då stimuleringen var på jämfört med av. Skillnaderna mellan och inom grupperna var inte signifikanta. Slutsats: Artikulatorisk precision och stabilitet påverkades efter DBS i form av bristande stabilitet, för kort slutningsrörelse och felaktig koordination av slutningsrörelsen. Detta resulterade i multipla explosioner och uteblivna explosioner med olika effekter för elektrodlokalisationerna. / Background: Deep Brain Stimulation (DBS) in Subthalamicus Nucleus (STN) and Caudala zona incerta (cZi) have shown positive effects on motor symptoms in Parkinson‘s disease. Negative effects on speech after DBS has been noted including reduced articulatory precision. Reduced articulatory precision and stability affects the production of stop consonants and as a result, loss of burst or multiple burst can occur. Aim: To investigate articulatory precision and stability regarding the burst in stop consonants after DBS of STN or cZi. Method: The study included 19 patients with 9 patients stimulated in STN and 10 patientsin cZi. Speech recordings were made before surgery and one year after with stimulation ON and OFF. The stop consonants were divided into three categories, those with one burst, those with two or more bursts (multiple burst) and those with loss of burst. Hypothesis testing was done on the categorization of the stop consonants in and between the groups and between the stop consonants types. Results: Multiple burst increased in the cZi group and decreased in the STN group. Stop consonants with loss of burst increased in the STN group but decreased in the cZi group. For both groups multiple burst and stop consonants with loss of burst increased with stimulation on. The differences between and within the groups were not significant. Conclusion: Articulatory precision and stability were affected by DBS with decreased stability, shortened occlusion and incorrect coordination. As a result multiple burst and loss of burst occurred in both groups. / Speech, voice and swallowing outcomes after deep brain stimulation of the zona incerta and the pedunculopontine nucleus in Parkinson’s disease: Comparsion with stimulation of the subthalamic nucleus

Bakgrund. Parkinsons sjukdom (PS) behandlas bland annat med djup hjärnstimulering (DBS). Ett relativt outforskat område för stimulering är caudala zona incerta (cZi). Man har med denna metod sett förbättringar när det gäller rörelsehindrande symtom men viss försämring av talet har påvisats. Syfte. Denna studie syftade till att undersöka om cZi-DBS vid PS påverkar talförståeligheten samt om förståeligheten av talet påverkas vid tillagt bakgrundsljud. Metod. Talmaterial med lästa ord från 10 patienter med PS, pre- och postoperativt samlades in. Dessa ord spelades upp för 32 lyssnare från allmänheten som ortografiskt transkriberade dessa. På en del av talmaterialet lades ett bakgrundsljud till som kan liknas vid ett bibliotek. Lyssnarnas transkriptioner poängsattes och statistiska beräkningar genomfördes. Resultat. Totalpoängen var signifikant lägre med påslagen stimulering jämfört med avslagen stimulering, oavsett bakgrundsljud. I blocket utan bakgrundsljud fanns även signifikanta skillnader som visade lägre totalpoäng när stimuleringen var påslagen jämfört med innan operation. Resultaten var genomgående signifikant lägre vid tillagt bakgrundsljud jämfört med utan. Slutsatser. Det har skett en försämring av talförståelighet vid stimulering av cZi. Dessa fynd är värdefulla för all vårdpersonal som jobbar med personer som har PS och de som ska genomgå/har genomgått cZi-DBS. Det är viktigt att hitta en balans mellan förbättrad motorisk förmåga och försämrad talförståelighet för att varje individ ska uppnå en så bra livskvalitet som möjligt.

Bakgrund: Deep brain stimulation (DBS) i kaudala zona incerta (Zi) har en tremorreducerande effekt vid den neurologiska sjukdomen essentiell tremor (ET). Stimulering av Zi har även positiva effekter på rösttremor, men individuella variationer förekommer. Tidigare har främst effekten mellan på- och avslagen stimulering undersökts. Inga studier har jämfört effekten på rösttremor vid ökande nivåer av stimuleringsstyrka.   Mål: Att undersöka effekt på rösttremor vid ökande unilateral stimuleringsstyrka av DBS i Zi hos deltagare med ET. Samt att undersöka prevalens och att se vilken rösttremorreducerande effekt deltagarnas kliniska inställningar har.   Metod: Trettioåtta deltagare med DBS Zi, bedömdes vid tre tillstånd: utan stimulering (DBS OFF), med kliniska inställningar (DBS ON) samt med ökande stimuleringsstyrka, 0,5-4,5V (DBS+). Rösttremor bedömdes utifrån inspelningar av uthållna vokalproduktioner i programmet “Visual Sort and Rate Method” (VISOR). Vid bedömning skattades förekomst och grad av rösttremor hos deltagarna genom att deltagarens egna inspelningar jämfördes med varandra i VISOR.   Resultat: DBS Zi hade på gruppnivå en positiv effekt på rösttremor vid såväl DBS ON som vid DBS+. De individuella skillnaderna var dock stora. Flest antal deltagare blev rösttremorfria vid DBS ON och vid stimuleringsnivåerna 1,5V, 2,0V, 3,5V och 4,5V. Prevalensen av rösttremor var 71% (27 deltagare).   Slutsats: DBS Zi har på gruppnivå en positiv effekt på rösttremor. De kliniska inställningarna är stimuleringsnivån som flest deltagare blir rösttremorfria vid. Den individuella variationen gör att man inte kan förutse om en individ kommer att få reducerad rösttremor av DBS Zi. / Tal- och rösteffekter av djup hjärnstimulering hos patienter med ärftlig tremor

Dried blood spots is an alternative method to collect blood samples from research subjects. However, little is known about how hemoglobin and hematocrit affect bead-based multiplex assay performance. The purpose of this study was to determine how bead-based multiplex assays perform when analyzing dried blood spot samples. A series of four experiments outline the study each with a specific purpose. A total of 167 subject samples were collected and 92 different biomarkers were measured. Median fluorescence intensity results show a positive correlation between filtered and non-filtered samples. Utilizing a smaller quantity of sample results in a positive correlation to a larger sample. Removal of hemoglobin from the dried blood spot sample does not increase detection or concentration of biomarkers. Of the 92 different biomarkers measured 56 were detectable in 100-75% of the attempted samples. We conclude that blood biomarkers can be detected using bead-based multiplex assays. In addition, it is possible to utilize a smaller quantity of sample while avoiding the use of the entire sample, and maintaining a correlation to the total sample. While our method of hemoglobin was efficient it also removed the biomarkers we wished to analyze. Thus, an alternative method is necessary to determine if removing hemoglobin increases concentration of biomarkers. More research is necessary to determine if the biomarkers measured in this study can be measured over time or within an experimental model.

FM halftoning is increasingly popular with traditional analog offset lithographic printing processes. There is a desire to offer this capability with digital presses based on electrophotographic printing (EP) technologies. However, the inherent instability of the EP process challenges the achievement of satisfactory print quality with dispersed-dot, aperiodic halftoning. The direct binary search (DBS) algorithm is widely considered to represent the gold standard of dispersed-dot, aperiodic halftone image quality. In this paper, we continue our previous efforts to adapt DBS to use with the Indigo liquid EP printing technology. We describe a complete color management pipeline for halftoning with a PARAWACS matrix designed using DBS. For the first time, we show actual printed patches obtained using our process. Our gamut mapping is performed in the YyCxCz color space, and is image-dependent. It incorporates several stages of alignment between the input and output spaces, as well as several stages of compression. After the gamut mapping, we tessellate the output color space into six global tetrahedra that each share the neutral axis, as an edge. Then, we determine the Neugebauer Primary Area Coverage (NPAC) for each pixel in the image to be printed by tetrahedral interpolation from the four nearest neighbors in the inverse printer mapping table. These four nearest neighbors are chosen so that only four Neugebauer primaries are used to render each pixel.

<p>Deep brain stimulation (DBS) is a surgical treatment technique, which involves application of electrical pulses via electrodes inserted into the brain. Neurons, typically located in the basal ganglia network, are stimulated by the electrical field. DBS is currently widely used for symptomatically treating Parkinson’s disease patients and could potentially be used for a number of neurological diseases. In this study, computational modeling was used to simulate the electrical activity of neurons being affected by the electrical field, to gain better understanding of the mechanisms of DBS. The spatial and temporal distribution of the electrical field was coupled to a cable model representing a human myelinated axon. A passing fiber with ends infinitely far away was simulated. Results show that excitation threshold is highly dependent on the diameter of the fiber and the influence (threshold-distance and threshold-diameter relations) can be controlled to some extent, using charge-balanced biphasic pulses.</p>

Deep brain stimulation (DBS) is a surgical treatment technique, which involves application of electrical pulses via electrodes inserted into the brain. Neurons, typically located in the basal ganglia network, are stimulated by the electrical field. DBS is currently widely used for symptomatically treating Parkinson’s disease patients and could potentially be used for a number of neurological diseases. In this study, computational modeling was used to simulate the electrical activity of neurons being affected by the electrical field, to gain better understanding of the mechanisms of DBS. The spatial and temporal distribution of the electrical field was coupled to a cable model representing a human myelinated axon. A passing fiber with ends infinitely far away was simulated. Results show that excitation threshold is highly dependent on the diameter of the fiber and the influence (threshold-distance and threshold-diameter relations) can be controlled to some extent, using charge-balanced biphasic pulses.

Abstract Background Deep brain stimulation (DBS) is a viable surgical treatment method for Parkinson’s disease (PD). It has positive effects on the classical motor symptoms, but effects on speech and voice are not equally beneficial. The speech disorder related to PD is hypokinetic dysarthria, with impaired articulatory precision as a prominent symptom. Studies have shown effects on different aspects of speech due to DBS of the subthalamic nucleus (STN) but the effects of stimulation of the caudal zona incerta (cZi) are less explored. Aims The aim of the current study was to investigate the effect of STN-DBS and cZi-DBS on perceptually measured articulatory precision in PD patients. Method Read speech productions were collected from 19 DBS-treated PD patients, ten STN and nine cZi. The recordings were made before surgery and 12 months postoperatively with stimulator on and off. Levodopa medication was always on. From the reading passage, three-syllable words were selected and isolated. Articulatory precision of the words was rated in two different assessments; an overall rating of articulatory precision and an identification of occurring misarticulations. Results The results from the perceptual assessment showed a decrease in articulatory precision after surgery for both groups. The decrease was significant for the cZi group, but not for the STN group. There was no significant difference between the groups. The frequency of observed misarticulations increased as an effect of DBS for both patient groups, with significant increase for the STN group but not for the cZi group. There was no significant difference between the groups. The most commonly observed misarticulation categories were stop-plosive reduced in quality, fricative realized as other fricative and stop-plosive realized as fricative . Conclusions The results obtained in the current study show that STN-DBS and cZi-DBS may have adverse effects on articulatory precision in PD patients. Keywords Articulatory precision, Parkinson’s disease, DBS, STN, cZi

A method for extraction of proteins from dried blood spots (DBS) for analysis using Proseek is developed and evaluated. DBS, as sample format, possesses a number of desirable advantages over for example plasma samples. These advantages include for example minimal patient invasiveness, sampling simplicity and non regulated sample transportation. Highly reproducible quantitative detection of 92 proteins is demonstrated from a 1.2 mm in diameter DBS disk. The DBS inter spot analysis precision (7% coefficient of variance) is comparable to plasma inter assay precision (6% coefficient of variance). Coefficient of variance is the ratio between standard deviation to mean value for the analysed replicates. Proseek analysis of DBS could possibly reveal a unique opportunity to examine health related issues in extremely premature infants hopefully resulting in increased survival rates in the future.