Nasjonalt kompetansesenter for ultralyd og bildeveiledet behandling Nevrokirurgi

Nasjonalt kompetansesenter for ultralyd og bildeveiledet behandling Nevrokirurgi Tormod Selbekk Forskningsleder SINTEF

2 Noen av de som har bidratt mye på nevro... Mer en 23 personer bidrar: Christian Askeland (SINTEF), Janne Beate Bakeng (SINTEF), Erik Magnus Berntsen (St. Olavs), Reidar Brekken (SINTEF/NTNU), Lars Eirik Bø (SINTEF), Christensen Pål (røntgen, St. Olavs), Sasha Gulati (St. Olavs), Marianne Haugvold (St. Olavs), Toril Hernes (NTNU), Daniel Høyer Iversen (NTNU/SINTEF), Asgeir S. Jakola (St. Olavs Hospital), Tom Børge Johannesen (Kreftregisteret), Kjell Arne Kvistad (St. Olavs Hospital/NTNU), Kaja Kvåle (NTNU), Frank Lindseth (NTNU/SINTEF), Linda Mohrsen Nordtvedt (St. Olavs Hospital/NTNU), Ingerid Reinertsen (SINTEF), Lisa Milgård Sagberg (St. Olavs /NTNU), Tormod Selbekk (SINTEF), Erik Smistad (NTNU/SINTEF), Ole Vegard Solberg (SINTEF), Ole Solheim (NTNU/St. Olavs), Geirmund Unsgård (NTNU/St. Olavs), og mange flere.. Avlagte grader i 2013: Asgeir S. Jakola, PhD disputas mai 2013 Tormod Selbekk, PhD disputas mars 2013 Lisa M. Sagberg, MSc forsvart i 2013, søkt PhD-opptak Stipendiater/studenter: Lars Eirik Bø, SINTEF, ultralyd og registrering, spine, 2011. Erik Smistad. Medical Image Segmentation. Technological PhD candidate. Mohammad Mehdi. Medical Image Visualization. Technological PhD candidate. Daniel Høyer Iversen. Forbedret ultralyd angio, Technological PhD candidate Tord Øygard, Masterstudent, 3D rekonstruksjon Kaja Kvåle, Masterstudent, elastografi Anne Line Stensjøen, Forskerlinjestudent

Ultrasound and navigation technology 3

Hva forventes av/gjør et kompetansesenter? 5 A. Tjenester rettet mot helsepersonell Kurs i 3D ultralyd og nevronavigasjon Foredrag på fagkonferanser App med pasientkasuistikk - ultralydbilder Ultralydsimulator B. Tjenester rettet mot pasienter Nye nettsider under utvikling Teknologi brukes i pasientbehandling C. Forskning og metodeutvikling Teknologiutvikling Utprøvning i klinikk - pilotstudier D. Kvalitetskontroll og kvalitetstutvikling Kliniske studier

Tjenester rettet mot helsepersonell Kurs i 3D ultralyd og navigasjon 6 2-dagers kurs arrangert i Trondheim for 6. år på rad! Med deltaker fra annen helseregion (SØ)!

Kompetansespredning Utvikling av App for kompetansespredning 7 Laget første versjon gjennom et studentprosjekt Viderutvikling i år..

Kompetansespredning Pasientkasuistikker i database - aneurysme 8

Tjenester rettet mot andre forskere/helsepersonell 9 Kompetansespredning Direkte overføring av nevrooperasjon med 3D ultralyd til stor internasjonal sykehuskonferanse i Oslo Spectrum, og med deltakelse på stand (ca 1000 deltakere, 38nde world hospital congress) Bidrag til medisinsk museum og Kunnskapsportal (som skal utvikles videre på web) Bidrag i foredrag og på konferanser Database med pasientkasuistikker - innsamling av data Utvikling av App med pasientkasuistikker, 3D ultralyd (studentprosekt) Utvikling av ultralyd simulator for hjerne Film om ultralydveiledet nevrokirurgi - ligger på NTNUs YouTube kanal Vitenskapelige publiseringer...

Forskning og kompetansespredning 10 Publiserte artikler i 2013 Publiserte artikler: 1. Reinertsen I, Jakola AS, Selbekk T, Solheim O.Validation of model-guided placement of external ventricular drains.int J Comput Assist Radiol Surg. 2014 Jan 11. [Epub ahead of print] 2. Sagberg LM, Jakola AS, Solheim O. Quality of life assessed with EQ-5D in patients undergoing glioma surgery: What is the responsiveness and minimal clinically important difference? Qual Life Res. 2013 Dec 7 [Epub ahead of print] 2. Jakola AS, Moen KG, Solheim O, Kvistad KA. "No growth" on serial MRI scans of a low grade glioma? Acta Neurochir (Wien) 2013, 155(12):2243-4, doi: 10.1007/s00701-013-1914-7. Letter to editor 3. Jakola AS, Reinertsen I, Selbekk T, Solheim O, Lindseth F, Gulati S, Unsgård G. Three dimensional ultrasound guided placement of ventricular catheters; technical note. World Neurosurg. 2013 Aug 22. doi:pii: S1878-8750(13)01008-5. 10.1016/j.wneu.2013.08.021. 4. Jakola AS, Unsgård G, Myrmel KS, Kloster R, Torp SH, Losvik OK, Lindal S, Solheim O. Surgical strategy in grade II astrocytoma: a population-based analysis of survival and morbidity with a strategy of early resection as compared to watchful waiting. Acta Neurochir (Wien) 2013; 155(12):2227-35 5. Rao V, Klepstad P, Losvik OK, Solheim O. Confusion with cerebral perfusion pessure in a litterature review of current guidelines and survey of clinical practise. Scand J Trauma Resusc Emerg Med. 2013; 21(1):78 6. Jakola AS, Unsgård G, Kloster R, Solheim O. Diffuse low-grade gliomas. J Neurosurg. 2013 Nov; 119(5): 1354-5. Letter to editor 7. Weber C, Jakola AS, Gulati S, Nygaard OP, Solheim O.Evidence-based clinical management and utilization of new technology in European neurosurgery. Acta Neurochir (Wien). 2013 Apr;155(4):747-54. doi: 10.1007/ s00701-013-1640-1 8. Selbekk T, Jakola AS, Solheim O, Johansen TF, Lindseth F, Reinertsen I, Unsgård G. Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochirurgica 2013; 155(6): 973-980 9. Iversen DH, Lindseth F, Unsgaard G, Torp H, Lovstakken L. Model-based correction of velocity measurements in navigated 3-d ultrasound imaging during neurosurgical interventions. IEEE Trans Med Imaging. 2013 Sep;32(9): 1622-31. doi: 10.1109/TMI.2013.2261536. 10. Reinertsen I et al. Validation of model-guided placement of external ventricular drains. akseptert for publisering i IJCARS. 11. Jakola AS, Bartek J Jr, Mathiesen T. Venous complications in supracerebellar infratentorial approach. Acta Neurochir (Wien). 2013 Mar;155(3):477-8. doi: 10.1007/s00701-012-1614-8. Epub 2013 Jan 12. 12. Solheim O. et al. Effects of cerebral magnetic resonance imaging in outpatients on incidence and survival of Lærebokkapittel: Lindseth F, Langø T, Selbekk T, Hansen R, Reinertsen I, Askeland C, Solheim O, Unsgård G, Mårvik R, Hernes TAN. Ultrasound-based guidance and Therapy. Kapittel i Online Acess boken Advancements and Breakthroughs in Ultrasound Imaging, InTech. DOI: 10.5772/46053

ffect of unclear lies on lone. 3,4 ffected atients are bet-. 5,6 For til prosafe, 7,8 survival t transof the lack of of susone of neurorategies etween Results Forskning Initial og kompetansespredning biopsy ORIGINALalone CONTRIBUTION was carried out in 47 (71%) patients served by the center favoring biopsy and watchful waiting and in 12 (14%) patients served by the center favoring early resection (P.001). Median follow-up was 7.0 years (interquartile range, 4.5-10.9) at the center favoring biopsy and watchful waiting and 7.1 years (interquartile range, 4.2-9.9) at the center favoring early resection (P=.95). The 2 groups were comparable with respect to baseline parameters. Overall survival was significantly better with ONLINE FIRST early surgical resection (P=.01). Median survival was 5.9 years (95% CI, 4.5-7.3) with the approachcomparison favoring biopsy only ofwhile a Strategy median survival Favoring was not reached Early with the approach favoring Surgical early resection. Resection Estimated 5-year vs a survival Strategy was 60% Favoring (95% CI, 48%-72%) and 74% (95% CI, 64%-84%) for biopsy and watchful waiting and early resection, respectively. In an adjusted multivariable analysis the relative hazard ratio was 1.8 (95% Watchful Waiting in Low-Grade Gliomas CI, 1.1-2.9, P=.03) when treated at the center favoring biopsy and watchful waiting. Klinisk studie - sammen med UNN Asgeir S. Jakola, MD Kristin S. Myrmel, MD Roar Kloster, MD Sverre H. Torp, MD, PhD Sigurd Lindal, MD, PhD Geirmund Unsgård, MD, PhD Ole Solheim, MD, PhD THE DIFFUSE LOW-GRADE GLIOmas (LGGs) include World Health Organization (WHO) grade II astrocytomas, oligodendrogliomas, and oligoastrocytomas. 1 Due to diffuse brain infiltration, LGGs are usually not considered surgically curable. 2 In fact, the effect of surgery on survival remains unclear because current evidence relies on uncontrolled surgical series alone. 3,4 Such series can be much affected by selection bias since patients with favorable outcomes may fare better regardless of treatment. 5,6 For example, watchful waiting until progression has been reported safe, 7,8 while others report improved survival and delayed time to malignant transformation if total resection of the tumor is achieved. 9-13 Due to lack of better evidence, management of suspected LGGs has remained one of AuthorAffiliations:DepartmentofNeurosurgery,StOlavs University Hospital, Trondheim (Drs Jakola, Unsgård, and Solheim); MI Lab (Drs Jakola and Solheim), Departments of Neuroscience (Drs Jakola and Unsgård),andLaboratory Medicine, Children s and Women s Health (Dr Torp), Norwegian University of Science and Technology, Trondheim; Department of Pathology (Drs Myrmel and Lindal), and Department of Ophthalmology and Context There are no controlled studies on surgical treatment of diffuse low-grade gliomas (LGGs), and management is controversial. Objective To examine survival in population-based parallel cohorts of LGGs from 2 Norwegian university hospitals with different surgical treatment strategies. Design, Setting, and Patients Both neurosurgical departments are exclusive providers in adjacent geographical regions with regional referral practices. In hospital A diagnostic biopsies followed by a wait and scan approach has been favored (biopsy and watchful waiting), while early resections have been advocated in hospital B (early resection). Thus, the treatment strategy in individual patients has been highly dependent on the patient s residential address. Histopathology specimens from all adult patients diagnosed with LGG from 1998 through 2009 underwent a blinded histopathological review to ensure uniform classification and inclusion. Follow-up ended April 11, 2011. There were 153 patients (66 from the center favoring biopsy and watchful waiting and 87 from the center favoring early resection) with diffuse LGGs included. Main Outcome Measure The prespecified primary end point was overall survival based on regional comparisons without adjusting for administered treatment. Results Initial biopsy alone was carried out in 47 (71%) patients served by the center favoring biopsy and watchful waiting and in 12 (14%) patients served by the center favoring early resection (P.001). Median follow-up was 7.0 years (interquartile range, 4.5-10.9) at the center favoring biopsy and watchful waiting and 7.1 years (interquartile range, 4.2-9.9) at the center favoring early resection (P=.95). The 2 groups were comparable with respect to baseline parameters. Overall survival was significantly better with early surgical resection (P=.01). Median survival was 5.9 years (95% CI, 4.5-7.3) with the approach favoring biopsy only while median survival was not reached with the approach favoring early resection. Estimated 5-year survival was 60% (95% CI, 48%-72%) @ntnu.no). and 74% (95% CI, 64%-84%) for biopsy and watchful waiting and early resection, respectively. In an adjusted multivariable analysis the relative hazard ratio was 1.8 (95% CI, 1.1-2.9, P=.03) when treated at the center favoring biopsy and watchful waiting. Conclusions For patients in Norway with LGG, treatment at a center that favored early surgical resection was associated with better overall survival than treatment at a center that favored biopsy and watchful waiting. This survival benefit remained after adjusting for validated prognostic factors. JAMA. 2012;308(18):doi:10.1001/jama.2012.12807 www.jama.com Conclusions For patients in Norway with LGG, treatment at a center that favored early surgical resection was associated with better overall survival than treatment at a center that favored biopsy and watchful waiting. This survival benefit remained after adjusting for validated prognostic factors. JAMA. 2012;308(18):doi:10.1001/jama.2012.12807 www.jama.com Neurosurgery (Dr Kloster), University Hospital of Northern Norway, Tromsø; and National Centre of Competence in Ultrasound and Image-Guided Surgery, Trondheim (Drs Jakola, Unsgård, and Solheim), Norway. Corresponding Author: Asgeir Store Jakola, MD, Department of Neurosurgery, St Olavs University Hospital, N-7006, Trondheim, Norway (asgeir.s.jakola on. All rights reserved. JAMA, Published online October 25, 2012 E1 11

ORIGINAL CONTRIBUTION Klinisk studie - sammen med UNN 12 ONLINE FIRST Comparison of a Strategy Favoring Early Surgical Resection vs a Strategy Favoring Watchful Waiting in Low-Grade Gliomas SURGICAL RESECTION VS WAITING IN LOW-GRADE GLIOMAS Survival, % Asgeir S. Jakola, MD Context There are no controlled studies on surgical treatment of diffuse low-grade Kristin S. Myrmel, MD gliomas (LGGs), and management is controversial. Roar Figure Kloster, 3. MD Survival When Treated in Accordance With Favored Strategy Objective To examine survival in population-based parallel cohorts of LGGs from 2 Sverre H. Torp, MD, PhD Norwegian university hospitals with different surgical treatment strategies. 100 Sigurd Lindal, MD, PhD Design, Setting, Early andresections Patients (hospital Both B) neurosurgical departments are exclusive pro- in adjacent geographical regions with regional referral practices. In hospital A 90viders Geirmund Unsgård, MD, PhD diagnostic biopsies followed by a wait and scan approach has been favored (biopsy 80 Ole Solheim, MD, PhD and watchful waiting), while early resections have been advocated in hospital B (early 70resection). Thus, the treatment strategy in individual patients has been highly dependent on the patient s residential address. Histopathology specimens from all adult pa- THE DIFFUSE LOW-GRADE GLIOmas (LGGs) include World tients diagnosed with LGG from 1998 through 2009 underwent a blinded histopatho- 60 Health Organization (WHO) 50logical review to ensure uniform classification and inclusion. Follow-up ended April grade II astrocytomas, oligodendrogliomas, and oligoastrocyto- 4011, 2011. There were 153 patients (66 from the center favoring biopsy and watchful waiting and 87 from the center favoring early resection) with diffuse LGGs included. 30 mas. 1 Due to diffuse brain infiltration, Main Outcome Measure The prespecified primary end point was overall survival LGGs are usually not considered surgically curable. 2 waiting (hospital A) 20based on regional comparisons Biopsy and watchful without adjusting for administered treatment. In fact, the effect of 10Results Initial biopsy alone was carried out in 47 (71%) patients served by the center surgery on survival remains unclear favoring Log-rank biopsy P <.001 and watchful waiting and in 12 (14%) patients served by the center favoring 0 early2 resection 4 (P.001). 6 Median8 follow-up 10 was 7.0 years (interquartile range, 0 because current evidence relies on uncontrolled surgical series alone. 3,4 4.5-10.9) at the center favoring biopsy and watchful waiting and 7.1 years (interquartile Time After Initial Surgery, y range, 4.2-9.9) at the center favoring early resection (P=.95). The 2 groups were comparable with respect to baseline parameters. Overall survival was significantly better with Such series can beno. much of patients affected at risk by selection bias since Biopsypatients early 47 surgical 30 resection 23 (P=.01). 14 Median 6survival was 3 5.9 years (95% CI, 4.5-7.3) with with favorable outcomes Resection may fare better regardless of treatment. 5,6 For proach favoring early resection. Estimated 5-year survival was 60% (95% CI, 48%-72%) the 75 approach 67 favoring 48 biopsy 39 only while22median 13 survival was not reached with the ap- example, This analysis watchful excludes waiting patients untilwho progressiocluding the has19 been patients reported with initial safe, resections 7,8 spectively. at hospital In anaadjusted and themultivariable 12 patients analysis who were theonly relative initially hazard biopsied ratio was 1.8 (95% initially andreceived 74% (95% treatment CI, 64%-84%) different forfrom biopsy the and local watchful favored waiting strategy and early (ex- resection, re- while at hospital others B). report A survival improved benefit survival of resection CI, 1.1-2.9, was seen P=.03) withwhen median treated survival at the of center 5.8 years favoring (95% biopsy CI, 3.0-8.7) and watchful waiting. and hospital delayed A while time to median malignant survival transformation if total resection of the early surgical resection was associated with better overall survival than treatment at a was not Conclusions reached at hospital For patients B (P.001). in Norway Shaded with areas LGG, indicate treatment 95% at acis. center that favored tumor is achieved. 9-13 Due to lack of center that favored biopsy and watchful waiting. This survival benefit remained after better evidence, management of suspected LGGs has remained one of JAMA. 2012;308(18):doi:10.1001/jama.2012.12807 adjusting for validated prognostic factors. Until now, the evidence concerning hard clinical end point, by making re- www.jama.com characteristics together with surgical results in terms of resection grades and complication rates. Nevertheless, based on the observed regional survival difference in the present study, both involved centers now advocate early resections as the initial recommendation in most patients. Most patients with suspected LGG have normal activity at the time of diagnosis with a reasonably long life expectancy regardless of treatment. The perceived risks of early and aggressive surgery can therefore seem unwarranted for both patients and physicians. In the present study, the survival difference between hospitals increased over time with an estimated absolute survival difference of 14% at 5yearsthatincreasedto24%at7years from diagnosis. Since most deaths from brain tumors are preceded by progressive symptoms, the possible early ad-

13 FOR og kompetansespredning Hvordan kan FOR bidra til å fremme kompetansespredning? Regionalt Nasjonalt Internasjonalt

14 Forskningsaktiviteter Hjernekirurgi Kliniske studier, QoL Klinisk utprøvning av ny ultralydvæske (kontaktmedium) Ultralyd angio i vaskulærkirurgi 3D ultralydveiledet innleggelse av ventrikkeldren 2D og 3D ultralyd i hypofysekirurgi Spinalkirurgi Ultralyd til MR registrering for nivådiagnostikk - metodeutvikling (BIA VIRTUS - sammen med OUS og UNN) Utprøvning av ultralyd i prolapskirurgi Ny post doc: Alfonso Rodriguez Molares - nummeriske metoder Forskning og teknologiutvikling Brain shift corrections - utprøvning av ulike metoder i klinikk Modellbasert metode for veiledning av ventrikkeldren Ultralydsimulering Ultralyd elastografi (master-avhandling)

Forskning og metodeutvikling 15 Hvordan forbedre ultralydbildene? Opphav til støy i ultralydbilder: Ulik dempning av lyd i hjernevev og fysiologisk saltvann

Forskning og metodeutvikling Ny «ultralydvæske» for nevrokirurgi Samme akustiske egenskaper som hjernevev (omtrent) 16 NaCl Ultralydvæske

Forskning og metodeutvikling Ny «ultralydvæske» for nevrokirurgi Historikk - Dyreforsøk gjennomført mai 2012 17

Forskning og metodeutvikling Ny «ultralydvæske» for nevrokirurgi Prøvd ut på 2 pasienter i 2013-13 pasienter gjenstår 18

Forskning og metodeutvikling 19 Ryggkirurgi - registrering Kan man bruke ultralyd for å finne riktig skivenivå for operasjon? Kan man bruke ultralyd for å registrere preoperative MR bilder til pasienten for navigasjonsformål? Registration of MR Images to Ultrasound Images of the Spine 7 Fig. 3. The ultrasound (blue) and MR (red) surfaces after the initial alignment (left) and after the final registration (right). Gryende samarbeid med University of British Columbia Synergi med BIA-Virtus prosjektet - hvor UNN og OUS deltar

Forskning og metodeutvikling 20 Simulering av ultralyd fra MR bilder

Forskning og metodeutvikling 21 Simulering av ultralyd fra MR bilder

22 FOR og forskning Hvordan kan FOR bidra til å fremme forskning? Klinisk Teknologisk På høyt nivå..

Takk for oppmerksomheten 23

Planer for 2014 Hjernekirurgi: Vaskulærkirurgi: Optimalisering av 3D scan-konvertering for angiodata. Avhengig av godkjenning av GE for innhenting av data. Vaskulærkirurgi: Klinisk artikkel, 30 pasienter med AVM operert med 3D ultralyd Vaskulærkirurgi: Implementere i CustusX metode for visualisere blodstrømsretning i sanntids 2D ultralyd over på segmenterte 3D vaskulærstrukturer, og klinisk utprøvning (1 artikkel). Ventrikkeldren: Gjennomføre klinisk verifisering av 3D ultralyd-veiledet innsetting av ventrikkeldren. Forberede multisenterstudie. Hypofysesvulster: Klinisk utprøvning av 2D + 3D ultralyd i hypofysekirurgi med 2 forskjellige ultralydprober (2 artikler) Hjernesvulster: Fortsette klinisk utprøvning av ny akustisk koplingsvæske på pasienter med glioblastom, samt formidle resultatene av studiet (artikkel). Korrigering av skift: Prøve ut metode for skift-korrigering av MR-bilder (2 artikler) Ultralyd elastografi: Igangsette nytt klinisk studium for 3D elastografi av hjernesvulster, samt gjennomgang av tidligere data tatt mot slutten av operasjonen (artikkel) Fortsette innsamling av pasientdata og analyser for kliniske studier angående o Livskvalitet for pasienter operert med hjernesvulster (2 artikler) o Analyse av reseksjonsgrad for lavgradige svulster operert v.h.a. 3D ultralyd (1 artikkel) o Ultralyd i aneurysmekirurgi o Endokrinologisk evaluering av pasienter operert for hypofysesvulst - med og uten intraoperativ ultralyd avbildning o Case - control studie: betydningen av sirkulasjonsforandringer som årsak til nevrologiske utfall etter hjernesvulstkirurgi (artikkel) o Vekstdynamikk (doblingstid) hos glioblastom som prognostisk faktor (2 artikler) 24

Planer for 2014 Ryggkirurgi: Registreringsmetoder: evaluere metode for registrering av ultralyd mot modell av ryggsøyla, i samarbeid med University of British Columbia. Utprøvning av ultralydprober (hypofyseprobe og borehulls-probe) i prolapskirurgi Hyppighet av spinale svulstoperasjoner vs. tetthet av MR-scannere i befolkningen (1 artikkel) 25 Antall planlagte artikler innsendt 2014: 13

Resultatmål for nevrokirurgi 26 Bygge opp og formidle kompetanse: Vitenskapelig arbeid - minst 11 artikler Overvåke og formidle behandlingsresultater: Minst ett review som tar for seg behandling i nevrokirurgi - klinisk eller teknologisk (Kvalitetsregister - må sjekke hvor mye arbeid det involverer) Delta i forskning og forskningsnettverk Få til en studie i 2014 i samarbeid med et annet Universitetssykehus Bidra i relevant undervisning Bidra med foredrag - 2 på kirurgisk høstmøte Ett innlegg på EANS Veiledning, kunnskap og kompetansespredning Kurs: 2-dagers kurs i ultralyd og navigasjon, lage kursopplegg for beitostølen Simulator - ultralydsimulator for trening på tolkning av ultralydbilder: 1 stk for gliomer App - database med pasientkasuistikker - 2 kasuistikker for de mest vanlige svulster - tilgjengelig i App Store Implementering av nasjonale retningslinjer og kunnskapsbasert praksis (Må baseres på resultater fra kliniske studier og review studier) Retningslinjer for behandling av lavgradige svulster - start i 2014

Kompetansesprednin 27 Kompetanseutvikling Delta i internasjonale forskningsnettverk Gjøre forskning - publisere i høyt rangerte tidsskrift Kompetansespredning Kurs 2 dagers praktisk kurs Kurs/stand på beitostølen - utvikle kurskonsept Foredrag Publikasjoner