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Joan Carles Soliva Vila Cognitive Neuroscience Research Unit (URNC)

Volumetric MR analysis of the caudate nucleus: a proposal for a diagnostic test in pediatric attention/deficit hyperactivity disorder. Joan Carles Soliva Vila Cognitive Neuroscience Research Unit (URNC) Dept . of Psychiatry . Autonomous University of Barcelona (UAB). Introduction.

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Joan Carles Soliva Vila Cognitive Neuroscience Research Unit (URNC)

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  1. Volumetric MR analysis of the caudate nucleus: a proposal for a diagnostic test in pediatricattention/deficit hyperactivity disorder Joan Carles Soliva Vila CognitiveNeuroscienceResearchUnit (URNC) Dept. of Psychiatry. AutonomousUniversity of Barcelona (UAB)

  2. Introduction • Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in childhood • Between 8-12 % of the pediatric population • Half of children with ADHD will display the disorder in adulthood • The diagnosis is made according to the DSM-IV-TR

  3. Introduction:DSM-IV-TR criteria • Six or more symptoms of inattention have been present for at least 6 months to a point that is disruptive and inappropriate for developmental level • Six or more symptoms of hyperactivity-impulsivity have been present for at least 6 months to an extent that is disruptive and inappropriate for developmental level • Some symptoms that cause impairment were present before age 7 years • Some impairment from the symptoms is present in two or more settings (e.g. at school/work and at home) • There must be clear evidence of significant impairment in social, school, or work functioning

  4. Introduction • Difficulties arise when the clinician needs to distinguish ADHD from a normal developmental level of inattention, impulsivity and hyperactivity • Further difficulties surface when one attempts to integrate diagnostic data culled from different informants

  5. Introduction • A growing number of morphometric brain magnetic resonance imaging (MRI) studies show neuroanatomical abnormalities in pediatric ADHD • Our group using a ROI-based methodology and a new semi-automated caudate-nucleus segmentation procedure has replicated right caudate volume abnormalities (Trèmols et al., 2008) reported in nearly all (3 out of 4) caudate-nucleus morphometric MRI studies with an appropriate sample size (n>30)

  6. Introduction • In addition, we reported a significant decreased volume of the right caudate-nucleus body, with a medium effect size • We hypothesize that a decreased normalized right caudate-body volume could be found in the ADHD pediatric population.

  7. Objective • To test this hypothesis and to determine the diagnostic accuracy of quantitative MR imaging in diagnosing pediatric ADHD

  8. Methods: Participants • 39 ADHD childreendiagnosedaccording to DSM-IV-TR • 39 IQ-matched controls • ADHD subjects were receiving stimulant medication (methylphenidate) and were considered by their physicians ,parents, and teachers to have a positive response

  9. Methods: MR imaging • MRI examination with a 1.5 T system (Signa, General Electric, Milwaukee, USA) • FSPGR-T1 3D axial sequence (TR=13.2 ms; TE=4.2 ms; FA=15; NEX=1; 256x256 matrix), with 2 mm partitions • FSE-DP-T2 axial sequence (TR=3980 ms; TE=20/100 ms; NEX= 2; 512x512 matrix), with 5 mm sections and 2 mm gap. • Two neuroradiologists, blind to the clinical diagnosis, independently read and analyzed all MR images • FSPGR-T1 3D was used for the morphometric analysis

  10. Methods:Caudate segmentation method • The first HEAD section to be measured is the first in which the caudate nucleus can be separated from the putamen nucleus, hence, excluding the ventral striatum • The last HEAD section is previous to that in which the caudate’santero-posterior diameter is more than two-times larger than the latero-lateral diameter • Alltheremaining dorsal sections are adscribedtothe BODY of thecaudatenucleus

  11. Methods: Statisticalanalyses • In order to counterbalance for different brain sizes, we normalized the rCBV using either the total bilateral caudate volume (tbCV) or the bilateral caudate body volume (bCBV) • A Student t-test was conducted between the two samples, targeting both tbCV-normalized and bCBV-normalized rCBV.

  12. Methods: Statisticalanalyses • We performed a ROC analysis • We divided our samples in two groups: • Training group: 20 cases and 20 IQ-matched controls • Test group: 19 cases and 19 IQ-matcehd controls • The area under the curve (AUC) and its confidence intervals were estimated using a non-parametrical method in the training group • The optimal cut-off value was selected in the training group using the sensitivity function

  13. Methods: Statisticalanalyses • To assess the inter-rater reliability of our caudate segmentation procedure the intra-class correlation coefficient (ICC) was used

  14. Results • The bCBV-normalized rCBV was found to be statistically different, in the two samples (t=3.16,p=0.001) with a high effect size (Δ=0.84)

  15. Results bCBV-normalized rCBV

  16. Results • The ROC analysis yielded an AUC=0.84 (CI0.95: 0.69 to 0.94) and Z=5.37 (p=0.001). • The optimal cut-off value (OCOV) was: OCOV≤ 0.4818 • It provided a sensitivity of 60.00% (CI0.95: 36.10% to 80.00%) and the specificity of 95.00% (CI0.95:75.10% to 99.20%)

  17. Results Empirical ROC analysis

  18. Results Predictive values at different levels of prevalence

  19. Conclusions • We believe that quantitative MRI imaging, employing the bCBV-normalized rCBV obtained by our segmentation procedure, may play a role as an ancillary test to assist in the diagnosis of ADHDin the pediatric population

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