VOLUME 5 / NUMBER 1 SPRING 2011

The Official NewsleTTer Of The americaN sOcieTy Of PediaTric NeurOradiOlOgy YRATIONS CLINICAL INSIGHTS INTRODUCTION By Gisele Ishak, M.D. and Dan Doherty, M.D., Ph.D. Seattle Children’s Hospital and University of Washington Welcome to this latest edition of Gyrations. Drs. Gisele Ishak and Dan THE MOLAR TOOTH SIGN (MTS): Doherty contribute to the Clinical JOUBERT SYNDROME AND RELATED DISORDERS Insight column an update on the devel - oping understanding of the so-called the diverse and overlapping clinical features Introduction Molar Tooth Malformation, and the now In 1969, Marie Joubert et al, first de - seen in patients. Other ciliopathies include termed Joubert Syndrome Related scribed Joubert syndrome in four siblings polycystic kidney disease, NPH, some forms Disorders. The ever-increasing under - with cerebellar vermis agenesis, ataxia, of retinal dystrophy, as well as Meckel (MKS), standing of genetic and molecular ele - episodic tachypnea, abnormal eye move - Bardet-Biedl, Jeune, Alström, Usher and ments of development demand our ment and intellectual disability. With the ad - Sensenbrenner syndromes. Genetic and clin - increasing knowledge of the imaging vent of cross sectional imaging a ical overlap may be seen: as noted above, phenotype-genotype correlations. Drs. pathognomonic midbrain-hindbrain mal- JSRD are caused by >10 different genes, Korgun Koral and Linda Heier pro - formation, the molar tooth sign (MTS), was while each gene (e.g. CEP290) can cause vide an article outlining how, in their in - described first in Joubert syndrome and sub - multiple syndromes (e.g. MKS, JSRD and iso - stitutions, they have altered imaging management of hydrocephalus to fol - sequently in several other conditions. lated retinal dystrophy). low the ALARA principles. We hope this Recently, the term “Joubert syndrome and Imaging and pathology: can help further the mission within the related disorders” (JSRD) has been adopted pediatric world to reduce radiation ex - The essential features of the MTS are to describe all disorders presenting with MTS posure in children. Drs. Paritosh Khanna seen on axial images (Figure 1), and include on brain imaging, including COACH and Andrew Poliakov then take us (Cerebellar vermis hypoplasia, Oligophrenia, vermis hypoplasia and thick, elongated and through some developing applications Ataxia, Coloboma, and Hepatic fibrosis), horizontal superior cerebellar peduncles of fMRI techniques that will have partic - Orofaciodigital type VI, Dekaban-Arima, (SCP). In addition, a narrow pontomesen - ular utility in pediatric patients. Finally, Malta, Senior-Løken (retinal dystrophy/ con - cephalic junction (=isthmus) with a deep Dr. Marv Nelson has again contributed genital retinal blindness and nephronophthi - interpeduncular (IP) fossa is often seen, and another Retzius Anatomy quiz for our sis - NPH) and other Cerebello-Oculo-Renal horizontal (but not thick) SCP have been de - entertainment and edification. syndromes (CORS). scribed in a “mild” MTS, usually seen with JSRD are clinically heterogeneous condi - homozogous NPHP1 mutations (Figure 2). Respectfully, tions characterized by core features of hypo - Sometimes, the MTS is not obvious in a Dennis Shaw, M.D. tonia, ataxia, intellectual disability and single axial image, so it is essential to look for Seattle Children’s Hospital variable involvement of the retina, kidney, the component features in all three planes. Seattle, Washington liver and other tissues/organs in subsets of On sagittal images, the roof of the fourth patients. The prevalence of JSRD has been ventricle is oriented more horizontally and estimated to be ~1/100,000 live births; how - the fastigium is positioned more superiorly ever, they are almost certainly under-diag - than usual (Figure 3). The fourth ventricle nosed. opens widely immediately distal to the aque - Ten genes responsible for JSRD have duct (rather than gradually tapering) and the A B C been described so far, accounting for ~50% foramen of Magendie is often enlarged. of patients. These genes encode proteins These findings reflect the horizontal SCP and that localize to the primary cilium and/or cerebellar vermian hypoplasia. The vermis basal body making JSRD part of an expand - varies from mildly hypoplastic to absent and ing group of conditions called “ciliopathies.” is more severe posteriorly than anteriorly, Primary cilia mediate mechano-, chemo- and often with dysplasia of the anterior vermis. light sensation, as well as major signal trans - Midline clefting is frequently seen rostrally on duction pathways, and cilia are involved in coronal images (Figure 4). Diffusion tensor imaging (DTI) demon - development and function oEf many tissues F and organs including the brain, retina, kid - ney, liver, skeleton and limbs, accounting for MTS continued on page 2 MTS continued from page 1 Kidney: Renal disease occurs in 25% THE RETZIUS of patients, ranging from nephronophthi - NEUROANATOMY strates lack of decussation of the SCP at sis (NPH), (most commonly) to cystic dys - the pontomesencephalic junction and plasia that overlaps with Meckel QUIZ #8 lack of decussation of the corticospinal syndrome. On ultrasound, NPH presents tracts at the medullary pyramids (Figure as normal-sized echogenic kidneys pro - 5). In addition, DTI can show lateraliza - gressing to small cysts at the corti - Name the structure with the arrow on tion of the deep cerebellar nuclei. comedullary junction with loss of this coronal section through the brain. Additional neuroimaging findings in - corticomedullary differentiation. CDK clude encephalocele, agenesis of the presents as large kidneys and multiple corpus callosum, ventriculomegaly, hy - cysts such as seen in Dekaban-Arima syn - drocephalus, posterior fossa cysts, cere - drome. bellar and cerebral heterotopia, Liver: Congenital hepatic fibrosis oc - polymicrogyria, hypothalamic hamar - curs in 18 % presenting as a spectrum of toma and absence of the pituitary gland. disease from persistently elevated Dysplasia of the deep cerebellar nuclei, transaminases, to hepatosplenomegaly, inferior olivary nuclei and multiple cranial to portal hypertension requiring por - nerve nuclei, and heterotopias of tosystemic shunting or resulting in upper Purkinje-like neurons have been noted in gastrointestinal bleeding. autopsy specimens. Skeletal: Polydactyly is seen in 16%. The pathology underlying the MTS Most commonly it is postaxial, followed appears to be an axon guidance defect, by preaxial and rarely mesaxial, variably as evidenced by the lack of decussation affecting the hands and feet. Recently, of the SCP. The absence of the crossing patients with both JSRD and Jeune as - ANSWER TO RETZIUS NEUROANATOMY fibers at the pontomesencenphalic junc - phyxiating thoracic dystrophy have been described based on clinical presentation QUIZ ON PAGE 5 tion likely also results in the decreased AP dimension of the isthmus and deep and plain films demonstrating shortened interpeduncular cistern. long bones and trident acetabulae, indi - cating that some genes may cause both Neurological features: of these conditions. Scoliosis due to hy - If not detected prenatally, patients potonia is also a reasonably frequent with JSRD typically present with signs of complication. cerebellum and brainstem dysfunction. Infantile hypotonia evolves into motor Diagnosis and Management: delays and ataxia later in life. Expressive After the diagnosis of MTS on brain communication (speech) is often more MRI, a search for multi-organ involvement severely affected than receptive commu - should be undertaken to allow early treat - nication due to the motor impairment. ment of medical complications. Cognitive outcomes range from severe Progressive renal, liver and retinal findings intellectual disability to typical range in - may remain asymptomatic for many years. IN THIS ISSUE: telligence. Eye movement abnormalities Guidelines for management of patients Introduction 1 are invariant and include oculomotor with JSRD have been developed including Clinical Insights: The Molar Tooth Sign (MTS): apraxia and nystagmus. Strabismus and yearly ophthalmologic evaluation, Joubert Syndrome and Related Disorders 1 ptosis are also common. Alternating renal/liver US, urinalysis, serum transamni - tachypnea/apnea is a distinctive feature nases, BUN and creatinine measurement. The Retzius Neuroanatomy Quiz 2 seen in many infants, reflecting disor - Liver MRI may be useful for diagnosis Minimizing Radiation Exposure in dered central respiratory control in the when liver fibrosis is suspected. Childhood Hydrosephalus: brainstem. Classification of JSRD is still evolving but it Low dose CT and limited MRI 4 is hoped that the emerging phenotype- Sedated Functional MRI (fMRI) and Functional Eye and extra central nervous genotype correlation may simplify the connectivity MRI (fcMRI) in Pediatric system involvement: quest for a causative gene in an affected Neuroimaging 6 Eye: Retinal dystrophy with visual loss individual in a purpose to prioritize testing Web Sites of Interest 5 is present in a ~25% of patients with and saving money and time. Meetings of Interest 8 JSRD and ranges from congenital blind - ness (Leber Congenital Amaurosis) to Genetic counseling and Message from the President 9 adult-onset nyctalopia (night blindness). prenatal diagnosis: In addition, chorioretinal colobomata are JSRD is predominantly autosomal EDITOR seen, particularly in patients with DENNIS SHAW, MD COACH syndrome. MTS continued on page 3

2 ASPNR ■ SPRING 2011 MTS continued from page 2 Conclusion: Further Reading The MTS on brain imaging is the pathog - 1. Sandeep Patel and A. James Barkovich recessive with rare instances of X-linked in - nomonic feature of JSRD. Though there have Analysis and Classification of Cerebellar heritance. The recurrence risk for a couple Malformations been multiple descriptions in the literature AJNR Am. J. Neuroradiol. , Aug 2002; 23: 1074 - with an affected child is generally 25%. since the initial imaging description of the MTS 1087. When the genetic cause is known, prena - in 1997, the imaging diagnosis is still missed at 2. A. Poretti, E. Boltshauser, T. Loenneker, E.M. tal diagnosis is feasible through chorionic Valente, F. Brancati, K. Il’Yasov, and T.A.G.M. times, particularly in milder cases. JSRD are Huisman villus or amniocentesis. When the genetic part of an expanding group of disorders, the Diffusion Tensor Imaging in Joubert Syndrome cause is not known, fetal MRI is the ciliopathies, caused by defects in proteins that AJNR Am. J. Neuroradiol. , Nov 2007; 28: 1929 – 1933 method of choice for the diagnosis of pos - localize to the primary cilium and basal bodies. 3. S.N. Saleem and M.S. Zaki terior fossa malformations. The MTS has Diagnosis of a JSRD has implications for diag - Role of MR Imaging in Prenatal Diagnosis of been described as early as 22 weeks ges - nostic work-up to identify retinal, kidney and Pregnancies at Risk for Joubert Syndrome and tation, and measurements at the pon - liver complications, as well as for genetic test - Related Cerebellar Disorders AJNR Am. J. Neuroradiol. , Mar 2010; 31: 424 – tomesencephalic junction may also ing and recurrence risk. Recognition of the 429 enhance diagnostic accuracy; however, MTS is essential for the early identification of 4. Jose L. Badano,1 Norimasa Mitsuma,1 Phil L. the sensitivity and specificity of fetal MRI these patients to allow early treatment of med - Beales,3 and Nicholas Katsanis1,2 The Ciliopathies: An Emerging Class of Human for diagnosing JSRD have not been sys - ical complications and allow for informed re - Genetic Disorders tematically evaluated. For a couple who productive decision-making. Annual Review of Genomics and Human has already had a child with JSRD, vermis Genetics , Vol. 7: 125-148 DOI: 10.1146/an - nurev.genom.7.080505.115610 hypoplasia is the only constant feature 5. Signs in Imaging: Peter McGraw The Molar that can be detected in affected fetuses, Tooth Sign Radiology December 2003 229:671- but encephalocele, polydactyly, kidney 672; DOI:10.1148/radiol.2293020764 cysts and/or abnormal breathing pattern can aid in the imaging diagnosis.

Figure 1. Axial T2 section through the mid brain demonstrating the MTS with thickened horizontally orientated SCP and deep inter pe - duncular cistern as well as dysplastic cerebellar vermis and hemi - spheres.

Figure 2. Axial T2 section through the midbrain showing mild MTS FIG. 1 FIG. 2 with elongated, horizontal but thin SCP and deformed fourth ventri - cle.

Figure 3. Sagittal T1 illustrating deformity of the fourth ventricle with horizontal SCP, elevated fastigium, hypoplastic vermis, and narrow isthmus.

Figure 4. Coronal T2 demonstrating cleft in the superior vermis.

Figure 5. Color-coded FA-maps at the level of the superior cerebellar peduncles.

Figure 5A. In a normal case the fibers within the superior cerebellar peduncles have a slight vertical orientation, characterized by a blue FIG. 3 FIG. 4 color coding on color coded FA-maps, confirming the vertical orienta - tion of the fibers within the superior cerebellar peduncles. Normal SCP decussation (appearing red) is seen at the level of the pontomes - encephalic junction.

Figure 5B. In JS, the fibers in the superior cerebellar peduncles have a more horizontal orientation on color vector DTI with absence of the SCP decussation, compared to a normal age matched control.

FIG.5A FIG.5B

SPRING 2011 ■ ASPNR 3 MINIMIZING RADIATION EXPOSURE IN CHILDHOOD HYDROCEPHALUS: Low Dose CT and Limited MRI Korgun Koral, M.D. and Linda A. Heier, M.D. UTSW Medical Center and Children’s Medical Center and NY Presbyterian Hospital/Cornell Campus

Beyond early childhood, when US can tomatically for every CT examination and quences has increased the ability to sub - be performed through the open fontanel, should be sent to PACS along with the stitute MRI for CT scans even in the CT has been the mainstay of ventricular study, to be part of the patient’s medical younger and less cooperative children. In evaluation in those with shunted hydro - record. Figure 1A is an example of the particular, single slice techniques with cephalus. Interest in reducing radiation, low-dose head CT image of a 5-year-old rapid filling of k-space, such as HASTE, particularly in those who will be getting re - girl with shunted hydrocephalus. A kVp of single shot TSE or SSFSE depending on peated scans through a lifetime, has lead 120 and mAs of 120 were used, generat - the manufacturer, can be used to reduce to using lower doses with CT and increas - ing a DLP of 230.21 (Figure 1B). When acquisitions to shorter than 1 second per ing use of MRI for monitoring ventricular DLP is multiplied by the conversion factor slice. Use of single slice techniques then size. The pediatric radiology community given in the Table for a 5 year old, the allows for repeating any individual slice has been on the forefront of reduction of product is the effective radiation dose in that has been affected by motion, without radiation dose in CT, fluoroscopy and radi - mSv, in this instance 0.92 mSv (230.21 x compromising the whole study. Though ography. The Image Gently™ campaign 0.0040). As seen in this example, even these rapid techniques do not provide the predates the increased public awareness using the low dose technique, a significant same tissue discrimination as standard se - generated by some recent publications amount of dose is delivered. The conver - quences, they are sufficient to evaluate and news reports. Patients with shunted sion factors decrease with increasing age, the ventricular size, and detect changes hydrocephalus are particularly susceptible indicating the greater effective radiation that reflect shunt dysfunction. to long term effects of ionizing radiation delivered by the same tube current para - Identification of the catheter itself can be not only because of the multiple imaging meters to a younger individual. For a problematic particularly with small ventric - studies they undergo over many years given effective radiation dose, the likeli - ular size, though this is generally not es - (probably throughout their lifetime), but hood of developing cancer is greater in sential. Using gradient echo rapid MRI also the imaging often begins very early, children and in adults. 2 Recently, a very techniques is reportedly superior in identi - many times in the newborn period. While useful CT dose and risk estimator has fication of the catheter4. For a rapid brain radiologists, pediatricians and the public been published by Alessio and Phillips 3 MRI, the time spent in the magnet is com - know that ionizing radiation is particularly and is available at http://faculty.washing - parable to CT scanning. deleterious in childhood, most are still un - ton.edu/aalessio/doserisk2 . One strategy in the younger child is to aware of the orders of magnitude. Rapid MRI technique, in lieu of CT, is set up the sequence to run twice through Selection of approach to be employed gaining increasing acceptance to avoid all the head, typically requiring about 20 sec - to minimize radiation in the follow-up of ionizing radiation incurred during follow- onds each. In the infant, a feed and scan patients with hydrocephalus at any given up of hydrocephalus. The major limitation approach is often successful. With tod - point depends on the clinical questions to of MRI evaluation has been the length of dlers, some combination of caregiver be answered. The patient’s condition and time required for MRI, necessitating coop - comfort in the scanner, distraction such as ability to cooperate are important factors eration or sedation in younger children. in choosing the appropriate imaging The advent of more rapid imaging se - Minimizing Radiat. continued on page 5 modality. Using a low-dose CT technique is particularly applicable in the follow up of Region of Effective dose per DLP [mSv(mGy cm)-1] hydrocephalus because of the inherently body a a a a b great attenuation differences of cere - 0 year old 1 year old 5 year old 10 year old Adult brospinal fluid and brain parenchyma. Low Head and 0.013 0.0085 0.0057 0.0042 0.0031 dose CT protocols are available on the Neck Image Gently™ web site for different ven - dors ( www.imagegently.org ). Head 0.011 0.0067 0.0040 0.0032 0.0021 It is possible to calculate the effective dose delivered during a particular CT ex - Neck 0.017 0.012 0.011 0.0079 0.0059 amination. The conversion factors from the Table (adapted from Shrimpton et al 1, Table. Normalized values of effective dose per dose linear product (DLP) over various body re - with permission) can be utilized for this. gions and patient ages. (Adapted from reference 1, with permission). a. Data normalized to CTDIw measured in the 16 cm diameter CT dosimetry phantom. The dose linear product is generated au - b. Data for the head neck regions normalized to CTDIw in the 32 cm diameter CT dosimetry phantom.

4 ASPNR ■ SPRING 2011 Minimizing Radiat. continued from page 4 FIG. 1A FIG. 2 in scanner videos (and bribery as necessary) can be effec - tive. The MR technologist then reviews the images, and re - peats any levels where a slice was not obtained without motion contamination. Interpretation requires discernment as slices are at times not contiguous due to motion between slices or re - peated scans. Although some parenchymal abnormalities may be identified on rapid brain MRI, it is generally un - derstood these are examinations with low resolution. The cost is potentially an issue, but many institutions have ap - propriately adjusted the fee of such a rapid MR to nearly equal that of the non-contrast CT. It is also worth consideration of adding the disclaimer to all dictations that the examination is limited and of de - FIG. 1B creased sensitivity for detecting parenchymal abnormali - ties than that of a standard MRI examination, so that the unaware clinician does not presume a standard MRI has been performed.

Further Reading Figure 1A. Low dose CT with a kVP of 120 and mAs of 120. DLP was 230.21 re - sulting in an effective dose= 0.92 mSv in a 5-year-old female. 1. Shrimpton PC, Hillier MC, Lewis MA, et al. National survey of doses from CT in the UK: 2003. Br J Radiol 2006;79:968-980 Figure 1B. Low dose CT with a kVP of 120 and mAs of 120. DLP was 230.21 re - 2. Berrington de Gonzalez A, Mahesh M, Kim KP, et al. Projected sulting in an effective dose= 0.92 mSv in a 5-year-old female. cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med 2009;169:2071-2077 Figure 2. Axial SS TSE image (FOV= 24 cm, slice thickness= 4mm, 32 slices ob - 3. Alessio AM, Phillips GS. A pediatric CT dose and risk estimator. Pediatr Radiol 2010;40:1816-1821 tained in 23 seconds) of a 2-year-old female demonstrates good quality images 4. Miller JH, Walkiewicz T, Towbin RB, et al. Improved delineation of can be obtained without sedation. ventricular shunt catheters using fast steady-state gradient recalled- echo sequences in a rapid brain MR imaging protocol in nonsedated pediatric patients. AJNR Am J Neuroradiol 2010;31:430-435

WEBSITES OF INTEREST ANSWER TO RETZIUS NEUROANATOMY QUIZ #8

In this new feature we will highlight websites of potential inter - est to the pediatric neuroradiologist. As such, we solicit sites mem - Answer: The ansa lenticulari bers have found useful that we can pass along in subsequent issues. Discussion: Ansa is Latin for handle and, in anatomical terms, refers Pediatric brain myelination atlas: A downloadable atlas useful to something that makes an arc or a loop. Lenticularis for approximate evaluation of myelin maturity on multiple pulse se - refers to the lentiform nucleus. quences from 7 weeks preterm to 4 years of age. There are also other neuroradiology-related atlases that are available from this This white matter tract begins in the lateral segment of site. the medial globus pallidus, loops under the internal cap - sule, and terminates in the ventral anterior and ventral http://www.seattlechildrens.org/healthcare-professionals/edu - lateral nuclei of the ipsilateral thalamus. cation/radiology/pediatricbrainatlas/ In the 1950’s, this tract was ablated in an attempt to con - trol the tremors of Parkinson’s disease. This technique Pediatric CT dose estimator mentioned in the article by Drs. was quickly abandoned, when little positive effects and Koral and Heier of the current issue. This web-based tool estimates many complications followed the procedure. the effective dose based on DLP, age, and body region scanned. It also then gives an estimated additional lifetime risk of cancer and, Thank you to Dr. Marvin D. Nelson, Children's Hospital as is intended, to serve as an educational tool for radiologists and of Los Angeles for contibuting the Retzius Quiz. clinicians to better understand risks.

http://faculty.washington.edu/aalessio/doserisk2/

SPRING 2011 ■ ASPNR 5 SEDATED FUNCTIONAL MRI (fMRI) AND FUNCTIONAL CONNECTIVITY MRI (fcMRI) IN PEDIATRIC NEUROIMAGING Paritosh Khanna, M.D. and Andrew Poliakov, Ph.D. Seattle Children’s Hospital

Introduction is not random noise, but is specifically or - Data processing Functional MRI (fMRI) techniques ganized in the resting human brain has Post-processing of sedated block de - based on BOLD response to task para - opened new avenues in neuroimaging re - sign fMRI studies is done both with the digms have become established in clinical search. A growing number of studies use Siemens workstation and FSL software practice, particularly, for pre-operative lo - resting state fcMRI to study various neuro - (http://www.fmrib.ox.ac.uk/fsl ). FSL offers calization of sensory-motor regions and logical and psychiatric conditions, obtain flexible tools for examining the imaging language lateralization. More recently, diagnostic and prognostic information, data and performing advanced fMRI fMRI paradigms have exploited the obser - and assess treatment effects. Furthermore, analysis. vation that some BOLD responses can be sedation has been shown not to Functional MRI data post processing seen from sensory input even under anes - alter fcMRI data. A recent initiative from includes slice-timing correction, B0 un - thesia. This fact has allowed use of some the Human Connectome Project warping, motion correction, co-registra - fMRI testing in younger children and in (http://www.humanconnectomeproject.org /) tion with structural T1 images and other patients who are unable to partici - should further advance these collective standard space etc. Functional connectiv - pate in standard testing paradigms requir - efforts. ity analysis is performed as implemented ing patient cooperation. In this article we discuss the current in software released by 1000 Functional Functional connectivity MRI (fcMRI) or techniques and some applications we are Connectomes Project (http://www.nitrc.org/ resting state functional MRI is a technique using in sedated fMRI and resting state projects/fcon_1000/ ). From prior work that describes spontaneous and synchro - fcMRI. identifying regions that have been ob - nous modulations of activity in neural sys - served to cycle together seed regions tems, in the absence of specific Data acquisition have been defined which are then em - task-based stimulation, occurring in neural At our Institution, most fMRI is per - ployed using standard space coordinates. systems across like areas of both hemi - formed on a 3T (Siemens MAGNETOM Correlation maps for the individual sub - spheres of the cerebrum and cerebellum. Trio) system using 32-channel or 12-chan - jects are produced by extracting the Although more established in the adult nel head coils. Those requiring sedation BOLD time course from a seed region, population, this technique promises po - are imaged under general anesthesia. then computing the correlation coefficient tential applicability in pediatric neu - Structural data typically includes a high- between that signal time course and the roimaging especially in the patient who is resolution, sagittal T1-weighted magneti - signal time course from all other brain vox - unable to cooperate with task based para - zation-prepared gradient echo (e.g. els. The correlation maps are converted to digms. MPRAGE) sequence which is fused with normal distribution by ‘z-transform’ to ob - In contrast to paradigms including the functional imaging data. For more ad - tain z-score maps that are thresholded at a block-design approach which evaluate vanced analysis including fcMRI, structural Z value of 3.0 (Figures 1, 2 and 3). BOLD changes that occur in response to a images and BOLD data are coregistered task, fcMRI focuses on (BOLD) signal fluc - linearly to the standardized atlas space Current Applications and tuations that occur during rest. The study (MNI brain, Montreal Neurological Future Directions of synchronous BOLD activity arose from Institute). Many pediatric patients are unable to the observation that spontaneous fluctua - Functional data is acquired using a perform specific tasks, either related to tions measured in one somatomotor cor - gradient echo, echo-planar sequence sen - their developmental stage or to a disease tex are specifically correlated with sitive to BOLD contrast (TR 3 s, TE 30 ms; state. Sedated fMRI and fcMRI allows for spontaneous fluctuations in the contralat - flip angle 90°; 3 x 3x 3 mm voxels; FOV evaluation despite disease state or devel - eral somatomotor cortex and with medial 192 mm; 45 contiguous slices). opmental age by permitting data acquisi - motor areas in the absence of overt motor Task related sedated paradigms include tion from the most impaired subjects as behavior. Similar results have been found sensory stimulation of the hand (brushing) al - functional imaging data can be obtained in multiple other networks including visual, ternating with rest, passive finger movement from the sleeping, sedated or anes - auditory and language, dorsal and ventral and visual checkerboard flashing (through thetized child. This can virtually eliminate attention systems, corticothalamic circuits, closed eyelids).Typically a 4 minute fMRI ac - noise from motion. and a frontal opercular network that has quisition is performed with four active and The applicability of fcMRI is best ap - been related to stimulus salience. The ob - four rest periods of equal length. For resting preciated in the context of its advantages servation that spontaneous BOLD activity state studies, one 8-minute fMRI acquisition over task-based functional MRI (fMRI), ob - consisting of 160 time frames is utilized. fMRI and fcMRI continued on page 7

6 ASPNR ■ SPRING 2011 fMRI and fcMRI continued from page 6 hand, separate tasks and data acquisitions have to be utilized for each system being tested. tained in the non-sedated patient. FcMRI lends simplicity in per - Evaluation of mesial temporal and memory function: FcMRI formance of the study since no task presentation equipment or can potentially be useful in assessing disruption of connectivity in cooperation is required. This may be particularly useful in some epileptic patients with hippocampal sclerosis and memory disrup - clinical settings. tion. Comparison of connectivity patterns in control subjects with - Finally, reproducibility of task-based paradigms in longitudinal out hippocampal sclerosis with that of patients with memory studies such as are utilized for evaluating treatment effects and disruption and epilepsy due to sclerosis has been performed at disease progression can be confounded by unavoidable variation our institution. Preliminary results demonstrate bilateral and sym - in task performance and administration, which can be less of an metric connectivity of a ventral precuneus seed point with the issue employing fcMRI. fusiform gyri, parahippocampus and hippocampus in control sub - FcMRI does have some disadvantages. Relatively long scan jects and epilepsy patients without hippocampal sclerosis. In con - time compared to a single task related paradigm may be a limit - trast, patients with sclerosis exhibited an asymmetric pattern of ing factor in some instances. Relative complexity of data analysis connectivity (Figure 3), with decreased connectivity on the side ip - makes it more limited at present for routine clinical use. Also, the understanding of these resting state fluctuations and the signifi - fMRI and fcMRI continued on page 8 cance of changes in findings is still in evolution particularly in the context of clinical applicability. Reproducibility of fcMRI studies would be important if widespread clinical use is to be adopted. At this time, reproducibility of this technique may range from good to moderate, depending on the system studied. Pre-surgical: The commonest application of fMRI is to guide pre-surgical planning of patients undergoing epileptic focus or tumor resection, usually to identify sensory-motor regions and for language lateralization in order to preserve function of eloquent areas of the brain. Sensory task paradigms with fMRI, under sedation, can be used to map sensory cortex, and its relationship to underlying brain lesions under consideration for resection. Sedated fMRI and fcMRI can serve as mapping tools for placement of EEG recording Figure 2. FcMRI patterns in ACC. First row shows seed regions repre - grids, deep brain stimulators, and for transcranial magnetic stimu - senting the following neural systems: default (LP), dorsal attention lators. FcMRI also can be combined with EEG to identify seizure (FEF), visual (V2), somatomotor (SM), auditory (A1). Second row shows foci. FcMRI allows for evaluation of multiple neural systems pre- corresponding fcMRI patterns that exhibit remarkably bilateral patterns in homologous brain regions. operatively from a single dataset. For sedated fMRI on the other

A

B

Figure 3. FcMRI patterns in Epilepsy. Resting state data were analyzed for connectivity with a seed in the ventral precuneus and retrospenial cortex. Control subjects: bilateral and symmetric connectivity of the Figure 1. Functional MRI results obtained in patients under anesthe - seed with the fusiform gyri, parahippocampus and hippocampus (white sia with sensory stimulation. A. Passive finger movement of the right arrows). Epileptic patients with hippocampal sclerosis: asymmetric con - hand produced activation in perirolandic cortex. B. Flashing screen nectivity patterns with conspicuous decrease in the left hippocampal stimulus delivered through closed eyelids produced deactivation in and parahippocampal regions. primary visual areas.

SPRING 2011 ■ ASPNR 7 fMRI and fcMRI cont. from page 7 Further Reading 1. Souweidane MM, Kim KHS, McDowall silateral to seizure onset. R, Ruge MI, Lis E, Krol G, Hirsch J MEETINGS OF INTEREST Correlation between fcMRI pat - (1999) Brain Mapping in Sedated Infants and Young Children with terns, extent of hippocampal scle - Passive-Functional Magnetic Resonance American Society of Spine Radiology (ASSR) rosis and degree of memory Imaging Pediatric Neurosurgery , 30, no. (www.TheASSR.org) function disruption are subjects for 2: 86-92 The Waikiki EDITION – Honolulu, HI `2. Biswal B, Yetkin FZ, Haughton VM, further study. Hyde JS (1995). Functional connectivity 2011 Annual Symposium- February 23-26, 2011 Prediction of brain maturation: in the motor cortex of resting human Data from some researchers sug - brain using echo-planar MRI. Magn American Society of Functional Neuroradiology Reson Med 34:537–541. gests that there may be potential in (ASFNR) (www.asfnr.org) `3. Cordes D, Haughton VM, Arfanakis K Pointe Hilton Tapatio Cliffs Resort – Phoenix, AZ this technique to aid in the diagno - (2000). Mapping functionally related 5th Annual Meeting – March 2-4, 2011 sis of developmental delays and regions of brain with functional connectivity MRI (fcMR). Am J pediatric-onset neuropsychiatric Neuroradiol 21:1636–1644. European Society of Magnetic Resonance in conditions. Reliable changes in 4. Kiviniemi V, Jauhiainen J, Tervonen O, Neuropediatrics (ESMRN) (www.esmrn.com) human functional brain maturation et al (2000). Slow vasomotor fluctuation in fMRI of anesthetized child brain. Amsterdam, The Netherlands during development have been Magn Reson Med 44:373–378. 11th International Congress documented that aid in predictions 5. Fox MD, Snyder AZ, Vincent JL, et al March 24-26, 2011 about an individual’s brain matura - (2005). The human brain is intrinsically organized into dynamic, anticorrelated tion. International Society for Magnetic Resonance in functional networks. Proc Natl Acad Sci Miscellaneous: Resting state USA 102:9673–9678. Medicine (ISMRM) (www.ismrm.org) connectivity patterns have been 6. Fox MD, Raichle ME (2007). Montreal, Quebec, Canada studied in autism, depression, Spontaneous fluctuations in brain 19th Annual Meeting & Exhibition activity observed with functional May 7-13, 2011 Tourette syndrome and schizophre - magnetic resonance imaging. Nat Rev nia. The severity of these condi - Neurosci 8:700 –711. tions has been correlated with 7. Redcay E, Kennedy DP, Courchesne E European Society of Pediatric Radiology and The (2007). fMRI during natural sleep as a connectivity patterns, which poten - Society for Pediatric Radiology (pedrad.org) method to study brain function during Hilton London Metropole Hotel, London, UK tially could be used to subcatego - early childhood. Neuroimage . 38:696- IPR London 2011 rize patients within each disease 707. 6th Congress and Exhibition of the joint Societies of entity to derive prognostic informa - 8. Greicius MD, Kiviniemi V, Tervonen O, et al (2008). Persistent default-mode Paediatic Radiology tion and to monitor response to network connectivity during light May 27-31, 2011 treatment. sedation. H um Brain Mapp. 29(7):839- 47. 9. Fair DA, Cohen AL, Power JD, et al American Society of Neuroradiology (ASNR) Conclusion (2009). Functional brain networks (www.asnr.org) Sedated fMRI and sedated or develop from a “local to distributed” Washington State Convention Center – Seattle, WA awake fcMRI provide clinical pre- organization. PLoS Comput Biol. ASNR Foundation Symposium – June 4-5, 2011 5(5):e1000381. surgical information and insight 10. Fransson P, Skiöld B, Engström M, et al ASNR 49th Annual Meeting – June 6-9, 2011 * into the functional organization of (2009). Spontaneous brain activity in the *ASPNR’s program will be on June 8-9 the pediatric brain independent of newborn brain during natural sleep - an fMRI study in infants born at full term. American Society of Spine Radiology (ASSR) ability to co-operate, and raise in - Pediatr Res. 66:301-5. (www.TheASSR.org) teresting questions and challenges 11. Dosenbach NU, Nardos B, Cohen AL, NH Constanza Hotel – Barcelona, Spain for future work. Substantial et al (2010). Prediction of individual brain maturity using fMRI. Science 2nd Joint Meeting of ASSR and ESNR – July 1-3, 2011 progress has been made in recent 329:1358-61. years in our understanding of the 12. Power JD, Fair DA, Schlaggar BL, American Society of Head and Neck Radiology Petersen SE (2010). The development fundamental nature of sponta - (ASHNR) (www.ashnr.org) neous fluctuations of the BOLD sig - of human functional brain networks. Neuron. 67:735-48. Hotel del Coronado – Coronado, CA nal and underlying neuronal and 13. Fox MD, Greicius M (2010). Clinical 45th Annual Meeting – September 7-11, 2011 metabolic activity. Nevertheless, applications of resting state functional connectivity. certain basic questions remain in - Front Syst Neurosci. 17; Eastern Neuroradiological Society (ENRS) 4:19. completely addressed. Continual 14. Van Dijk KR, Hedden T, Venkataraman (www.enrs.org) improvements in data acquisition A, Intrinsic functional connectivity as a Chatham Bars Inn – Chatham, MA and analysis techniques are being tool for human connectomics: theory, Twenty-third Annual Meeting properties, and optimization. J September 15-17, 2011 evaluated for incorporation into Neurophysiol. 2010 Jan; 103(1):297- clinical use with particular applica - 321. Epub 2009 Nov 4. tions in the pediatric population. Western Neuroradiological Society (WNRS) (www.wnrs.org) Rancho Las Palmas Resort & Spa – Rancho Mirage, CA 45th Annual Meeting – October 20-24, 2011

8 ASPNR ■ SPRING 2011 MESSAGE FROM THE PRESIDENT PEDIATRIC NEURORADIOLOGY – QUID NOVI

BY TINA YOUNG POUSSAINT, M.D. Children’s HospitaL Boston, Massachusetts

Nearly 9 months since the ASPNR functional MR, and functional imaging will help us to detect and diagnose both program at the May 2010 Boston meeting techniques, such as magneto- acquired and congenital brain diseases in of the ASNR, there is perhaps no better encephalography (MEG), and magnetic their earliest stages. Collaborative work time in these days of winter to reflect on source imaging (MSI). In addition, we are with teams of physicians across medical our vibrant ASPNR. The ASPNR, as a encouraged by improvements in specialties to develop effective treatment constituent member of the ASNR, has computational methods and systems to plans and innovative research protocols fostered the emergence of pediatric analyze images coupled with higher field should follow. Our continued mission is neuroradiology as a distinct super- strength magnets that enable more also to support our members with specialty within neuroradiology. sophisticated imaging for clinical research. resources, namely: 1) opportunities for Radiologic imaging of the developing and Neuroimaging helps integrate the continuing medical and professional matured central nervous system is steadily neuroscience information from the education in pediatric neuroradiology; improving; it requires keeping up with laboratory and molecular biology to the 2) regular forums through which best neurologic advances from all perspectives bedside patient care. Molecular and practice can be communicated, discussed, to develop a finely-honed understanding metabolic imaging (including PET, with and debated; 3) access to current clinical of the imaging features of pediatric various novel radiopharmaceuticals) can and bench research through publications, diseases and anomalies of the CNS. aptly demonstrate cellular and subcellular abstracts, posters, conference pro- Today, we find ourselves at a medical processes, neural systems and neuronal ceedings, and lectures; 4) formal and and professional cross-road where the function. informal mechanisms for networking demands for imaging children to quickly Neurosciences advances have helped with peers and fostering research obtain an accurate diagnosis must be to frame content of the ASPNR program collaborations; and 5) a philosophy of balanced by the need to use the least for the June 2011 ASNR meeting in professional growth that encourages invasive methods including little ionizing Seattle. The 2011 ASPNR program members to represent the value of radiation, as low as reasonably achievable includes three scientific sessions: pediatric neuroradiology to medical care (ALARA), while maintaining diagnostic (1) Phakomatoses Update … a review of facilities, academic medical institutions, image quality. “Easier said, than done,” the clinical features, genetic testing, and medical schools across the country as as we know all too well, when nonspecific targeted molecular therapies and well as to the NIH and other related symptoms and signs may represent neuroimaging of the phakomatoses; scientific organizations. several illnesses, and many exams may be (2) Of Molecules and Morphology: We are a committed membership needed to arrive at a diagnosis – the Molecular Bases of CNS Malformation … equal to the challenges of an ambitious prospect of saving the life of an infant or lectures on: a) patterning of the cerebral agenda. Please reflect on how the ASPNR child assumes great urgency. cortex; b) the great forebrain can continue to improve. As President, I These very significant challenges commissures: development, anatomy and welcome your assistance as we embark on require a strong, positive response from misunderstanding; and c) embryogenesis this journey for the ASPNR. The ASPNR us, especially during this period of and malformations of the midbrain and website that is under construction will be neuroscience enlightenment, where there hindbrain; (3) Metabolic Diseases of of great utility to help in responding has been expansion of knowledge about Childhood … clinical features and positively to the challenges ahead. I need the development and function of the neurological presentation, genetic your support and encourage your nervous system, as well as its many approaches to diagnosis and imaging of attendance at the ASPNR program of the diseases and disorders. Advances in brain metabolic conditions; and the “ Interesting 49th ASNR Annual Meeting in Seattle. imaging technologies allow a more Case” Team Competition: Blue Stars vs. comprehensive means to investigate Red Stars – the annual array of interesting neurological disorders and diseases cases for experienced discussants. leading to improved diagnosis and We must continue our primary mission treatment. Information on metabolic and to champion pediatric neuroradiology for physiological processes may be obtained its crucial role in the lives of children by diffusion tensor imaging (DTI), diffusion afflicted with neurologic illnesses and source imaging (DSI), MR perfusion, disorders. The imaging tools and magnetic resonance spectroscopy (MRS), techniques that are now at our disposal

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