Diseases of the Brain, Head and Neck, Spine 2020–2023

This open access book offers an essential overview of brain, head and neck, and spine imaging. Over the last few years, there have been considerable advances in this area, driven by both clinical and technological developments. Written by leading international experts and teachers, the chapters are disease-oriented and cover all relevant imaging modalities, with a focus on magnetic resonance imaging and computed tomography. The book also includes a synopsis of pediatric imaging. IDKD books are rewritten (not merely updated) every four years, which means they offer a comprehensive review of the state-of-the-art in imaging. The book is clearly structured and features learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers navigate the text. It will particularly appeal to general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic expertise, as well as clinicians from other specialties who are interested in imaging for their patient care

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck

BACKGROUND: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF. MATERIALS AND METHODS: We compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (ve, Ktrans, kep) in muscle-located outside the radiation area-were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans. RESULTS: Several parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: ve (0.65, 0.74, 0.58, 0.32), Ktrans (0.30, 0.21, 0.13, 0.06), kep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs. CONCLUSION: Image-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area

Extracranial Soft-Tissue Tumors: Repeatability of Apparent Diffusion Coefficient Estimates from Diffusion-weighted MR Imaging.

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article

Extracranial soft-tissue Tumors: repeatability of apparent diffusion coefficient estimates from diffusion-weighted MR imaging

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%–6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = −0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies—a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations

Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy.

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy. © 2016. The Korean Society for Radiation Oncology.11Yscopu

Diffusionâ weighted imaging outside the brain: Consensus statement from an ISMRMâ sponsored workshop

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134160/1/jmri25196_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134160/2/jmri25196.pd

Radiation induced brain necrosis after proton therapy for head and neck cancer

Protonterapi gir reduksjon i normalvevsdoser sammenlignet med strålebehandling med fotoner, og det er antatt at dette vil resultere i en lavere forekomst av stråleinduserte seinskader. For å kompensere for en økt biologisk effektivitet av protoner benyttes en konstant verdi for den relative biologiske effektiviteten (RBE) som er satt til 1.1. Det er imidlertid kjent at RBE varierer blant annet med lineær energioverføring (LET), dose og strålesensitivitetsparameteren α/β. Et stort antall RBE-modeller basert på disse variablene har blitt utviklet for bedre å beskrive proton RBE. Klinisk er det manglende kunnskap om effekten av en variabel proton RBE, men det er sterke in vitro-bevis for en økning i RBE som en funksjon av LET. For kreft lokalisert i skallebasisregion kan strålebehandling medføre at deler av hjernen får høye stråledoser. Disse pasientene har derfor en livslang risiko for å utvikle stråleindusert hjernenekrose. Denne diagnosen stilles som oftest på grunnlag av MR-radiologi, typisk ser en kontrastoppladede lesjoner på T1-vektede sekvenser og økt intensitet på T2 sekvenser. I litteraturen er insidensen av disse bildeendringene (RAIC) godt beskrevet etter intensitetsmodulert strålebehandling (IMRT) for HNC, men det er begrenset antall studier på pasienter behandlet med protonterapi. Nylig har det kommet forskning som indikerer at RAIC forekommer hyppigere etter protonterapi. Det har blitt stilt en hypotese om at dette er relatert til økning i RBE på grunn av forhøyet LET i distale delen av protonstrålen. Målet med dette doktorgradsarbeidet var derfor å utforske risikofaktorer for utvikling av RAIC hos pasienter behandlet med protonterapi for hode-halskreft lokalisert i skallebaseregionen. Pasientene i studien hadde blitt behandlet med intensitetsmodulert protonterapi (IMPT) og/eller passiv teknikk (PSPT) ved MD Anderson Cancer Center mellom 2010 og 2018. I første artikkel ble insidens av RAIC undersøkt og dose grenser for å redusere risiko ble identifisert. Insidens av RAIC var 17% noe som samsvarte godt med det som har blitt funnet i andre studier etter protonterapi. Flertallet av disse ble behandlet for nasopharynx eller sinonasal kreft (77%). Det ble funnet lesjoner i temporallappene, frontallappen og i cerebellum, de fleste i kant eller så vidt overlappende med CTV. Ingen av pasientene hadde symptomer assosiert med hjernenekrose. Lesjoner var i progresjon hos 18% av pasientene. V67 Gy(RBE) < 0.2cc til hjerne be identifisert som den viktigste dose-variabelen for å begrense risikoen for å utvikle RAIC. I artikkel II var målet å undersøke hvordan RBE-variasjoner kan påvirke estimert risiko for å utvikle stråleindusert temporallappsnekrose. Monte Carlo-simuleringer ble brukt til å beregne variabel RBE-vektede doser (RWDVar) ved hjelp av to publiserte RBE-modeller. Vi fant at RWDVar var signifikant høyere enn doser kalkulert med RBE = 1.1 (RWDFix). Vi fant videre indikasjoner for at risikoen for å utvikle temporallappsnekrose kan bli undervurdert hvis dosegrenser vurderes basert på RWDFix. Maksimal dose til temporallappen var svært influert av variabel RBE, noe som resulterte i store usikkerheter og økning i estimert risiko, mens de andre undersøkte dosevariablene var mindre påvirket av variabel RBE. Resultatet fra denne studien viser at å inkludere RWDVar som en del av IMPT behandlingsplanevaluering kan gi verdifull klinisk informasjon når det gjelder beskyttelse av temporallappen. I artikkel III så vi etter korrelasjoner mellom områder med strålingsnekrose, dose og dose-gjennomsnittlig LET (LETd). Femten pasienter diagnostisert med RAIC som hadde blitt behandlet med IMPT ble inkludert i analysen. Nøyaktige dose- og LETd-fordelinger ble beregnet ved hjelp av Monte Carlo-simuleringer og ekstrahert på voxelnivå fra pasientenes behandlingsplaner. En logistisk regresjonsmodell som estimerer tilfeldige og faste effekter ble brukt i analysen. Analysen avdekket betydelige interpasient variasjoner, men allikevel en signifikant korrelasjon mellom økende LETd og regioner med RAIC. Resultatene våre antydet at LETd-effekten kan være av klinisk betydning for noen pasienter, og at LETd-vurdering i kliniske behandlingsplaner derfor bør tas i betraktning. Samlet sett har dette arbeidet gitt økt kunnskap om risiko for utvikling av stråleeffekter i hjernen etter protonterapi. Forekomsten av RAIC for hode-hals kreft i skallebasisregionen er sammenlignbar med det en har sett i andre protonserier. Våre funn tyder på at variabel RBE-relaterte usikkerheter og potensielle LETd-effekter kan være avgjørende og bør inngå som del av klinisk behandlingsplanevaluering. Selv om dette ofte vurderes implisitt ved protonterapi, bør av beregnings- og planleggingsverktøy basert på spesifikke LETd-data sammen med fysisk dose implementeres i klinisk praksis.With proton therapy, reduction in normal tissue doses is achievable with equal or better target dose conformity due to the Bragg Peak effect. The main rationale for proton therapy today is based on an assumption that this will translate into a more favorable treatment outcome, specifically in terms of lower normal tissue complication rates. However, proton therapy is accompanied with an inherent uncertainty in the actual biological dose delivered. It is well recognized that the constant Relative Biological Effectiveness (RBE) currently applied in clinical proton beams is a simplification of the reality; rather than being a fixed factor, RBE varies depending on several physical, biological and treatment related factors. A wide range of models derived from in-vitro data have been proposed to describe the variable RBE based on the Linear Energy Transfer (LET), dose and α/β. Clinically, the relationship between biological effect and variable RBE is not well understood, however there are strong in-vitro evidence for an increase in RBE as a function of LET. During radiotherapy for head and neck cancer (HNC) at the skull base region, patients may receive high radiation doses to parts of the brain and will therefore have a lifelong risk of developing radiation-induced brain necrosis. Patients are most commonly diagnosed on the basis of characteristic changes on Magnetic Resonance Images (MRI), including contrast enhanced lesions on T1-weighted sequences or hyperintensities on T2-weighted sequences. There are numerous publications addressing these radiation associate image changes (RAIC) after intensity modulated radiotherapy (IMRT) for HNC, however, there are limited number of studies in patients treated with proton therapy. Previous research in pediatric and adult patient cohorts treated for both intracranial and extracranial skull base tumors suggest that RAIC occur more frequently after proton therapy. It has been hypothesized that this may be explained by an increase in the LET at the distal part of the proton beam. The aim of this PhD work was to explore RAIC in patients treated with proton therapy for HNC at the skull base region. The patient material included a wide range of HNCs treated with intensity modulated proton therapy (IMPT) and/ or passive scattering proton therapy (PSPT) at MD Anderson Cancer Center between 2010 and 2018. In paper I, the incidence and patterns of RAIC were investigated, and practical brain dose constraints (RBE = 1.1) associated with RAIC were derived. The incidence of RAIC corresponded reasonably well with observed rates previously reported after proton therapy. During a median latency time of 24 months, RAIC were found on follow-up MRIs in 22 out of 127 patients (17%). The majority of the patients with RAIC were treated for nasopharyngeal or sinonasal cancers (77%). Lesions were found in the temporal lobes, frontal lobes and the cerebellum, typically outside or slightly overlapping with the CTV. All lesions were asymptomatic. On the last available follow-up MRI, 18% of the lesions were in progression, whereas 27% had resolved. RAIC was significantly associated with dosimetric variables only. Brain V67 Gy (RBE) < 0.2cc was identified as the most important dose volume threshold in order to limit risk of developing RAIC. In paper II, the aim was to investigate the influence of RBE variations on the assessment of risk of developing temporal lobe necrosis. The patient material included 45 patients treated with IMPT and who had a follow-up time of 24 months or longer. Image changes diagnosed radiation necrosis was observed in sixteen temporal lobes. Monte Carlo simulations were used to calculate RWDVar based on two previously published RBE models. The RWDVar was significantly increased compared to RWDFix. We further found indications that the risk of developing temporal lobe necrosis could be underestimated when evaluating dose constraints according to RWDFix. Dose-volume predictors with near-maximum doses were less influenced by RBE variations than the maximum dose. The result from this study suggests that including RWDVar as part of IMPT treatment plan evaluation may provide valuable clinical information in terms of temporal lobe protection. In paper III we looked for correlations between regions of radiation necrosis, dose and dose-averaged LET (LETd). Fifteen patients with RAIC who had been treated with IMPT were included in the analysis. Accurate dose- and LETd distributions were calculated using Monte Carlo simulations and extracted voxel-by-voxel from the patients’ treatment plans using an in-house developed MATLAB-script. Mixed effect logistic regression methodology were used for analysis. The analysis revealed substantial interpatient variations, however an overall significant correlation between increasing LETd and regions with RAIC. Our results suggested that the LETd effect could be of clinical significance for some patients and that LETd assessment in clinical treatment plans should therefore be taken into consideration. Overall, this work has provided increased knowledge on risk factors for development of radiation effects in the brain after proton therapy. Incidence rates of RAIC in HNC at the skull base are comparable to other proton series. Our findings suggest that variable RBE related uncertainties and potential LETd effects are essential to consider in clinical treatment plan evaluation. Although often considered implicitly in the mind of the clinician for proton therapy, continued evidence such as the current work may lead to changes in clinical practice, namely the implementation of computerized calculation and planning tools based on specifically LETd data along with physical dose.Doktorgradsavhandlin