Imaging of the Pediatric Brain, Spinal Cord and Muscle: Tools and Clinical Applications

Disclosure Information AACPDM 68th Annual Meeting September 10-13, 2014

Imaging of the pediatric brain, spinal cord • Speakers’ Names: Andrea Poretti, Avner Meoded and muscle: Tools and clinical applications and Alec Hoon Andrea Poretti, MD Avner Meoded, MD • Disclosure of Relevant Financial Relationships: Research Associate Research Associate Section of Pediatric Neuroradiology Section of Pediatric Neuroradiology We have no financial relationships to disclose The Johns Hopkins School of Medicine The Johns Hopkins School of Medicine Alec Hoon, MD • Disclosure of Off-Label and/or investigative uses: Associate Professor of Pediatrics We will not discuss off label use and/or The Johns Hopkins School of Medicine Director, Phelps Center investigational use in our presentation Kennedy Krieger Institute AACPDM 68th Annual Meeting, San Diego, September 10-13, 2014 ©AP ©AP

Course objectives

• The participant will: 1. Identify the principles of the various imaging modalities available to clinicians 2. Recognize clinical settings when specific imaging tools are appropriate/indicated 3. Recognize clinical applications of the imaging techniques 4. Consider the use of these techniques in his/her clinical practice

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Introduction Head Ultrasound

Pro Contra • Neuroimaging techniques: • No ionizing radiation • Age-dependent = only newborn – Conventional-anatomical: • No sedation + infants • US, CT, MRI: T1, T2, FLAIR, … • Bedside • Investigator dependent

• Relatively inexpensive • Limited for the evaluation of  • Serial imaging easy brain periphery abnormalities – Advanced-functional: at the brain convexity can be missed • DWI, DTI, SWI, 1H-MRS, …

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1 Head ultrasound

P R T E E T R E M R M

Venous hemorrhagic infarction with follow-up

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Head ultrasound Head ultrasound

Anterior fontanel Mastoid fontanel

Acute hypoxic-ischemic injury in a term neonate Cerebellar hemorrhage: Best seen on images through the mastoid fontanel ©AP ©AP

Head ultrasound Computed tomography (CT)

Pro Contra • Resistive index (RI) of the • Widely available • Limited ability to distinguish intracranial vasculature: • Rapid between tissues with subtle differences in densities – Correlates with brain perfusion • Usually no sedation – Measurement: Anterior • Ionizing radiation circulation (e.g. ACA) – Side effects (short/long term) – Normal values: 0.65-0.75 (term – Impact on developing brain neonates) – HIE: RI values ↓ (<0.5)  correlation with poor outcome CT should be used with caution in children and alternative imaging modalities should be used whenever possible

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2 CT: Indications CT: Calcifications

• Calcifications: – Congenital infections: CMV, Toxoplasmosis, … – Metabolic: Aicardi-Goutières syndrome, Cockayne syndrome, … – Brain tumors • Skull abnormalities: – Craniosynostosis – Trauma Confirmed congenital CMV infection

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Congenital CMV infection CT: Calcifications

Congenital toxoplasmosis infection Congenital HIV infection

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CT: Calcifications Conventional MRI: T1, T2

• T1 = Myelin-weighted • T2 = H20-weighted

– Myelin = bright – H20 = bright

– H20 = dark – Myelin = dark

Aicardi-Goutières syndrome

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3 Conventional MRI: T1 Conventional MRI: myelination

• Useful for delineation of anatomy • Unmyelinated white matter = H20 +++

CT T1 • Myelinated white matter = fat/myelin +++

• Bright on T1: T2w T1w T2w T1w T2w T1w – Blood (sub-acute hemorrhage) – Fat – Melanin – Contrast agent

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Conventional MRI: T1, T2 Conventional MRI: T1, T2

Patient Control Patient Control

Congenital Pelizaeus-Merzbacher disease

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Conventional MRI: T1, T2 Conventional MRI: T1, T2

Sequelae after acute neonatal hypoxic-ischemic injury Lissencephaly

posterior > anterior gradient ©AP ©AP

4 T1 + contrast agent

• Contrast agent = paramagnetic (T1-shortening  bright signal) Periventricular leukomalacia • Within brain tissue = abnormal • Enhancement = damage of the blood-brain barrier: – Brain tumors – Infections – Inflammations – … ©AP ©AP

T1 + contrast agent T1 + contrast agent

T2 T1c

T1+c

X-linked adrenoleukodystrophy

Neonatal HSV infection ©AP ©AP

FLAIR = FLuid Attenuated FLAIR Inversion Recovery FLAIR T2 H20-weighted + suppression of CSF = T2w image with dark CSF • Allows a better evaluation of the structure close to CSF spaces: – Periventricular white matter – Dentate nuclei – …

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5 FLAIR FLAIR

FLAIR T2 FLAIR T2

Late-infantile neuronal ceroid lipofuscinosis Vanishing white matter disease

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Magnetic resonance angiography MRA + MRV (MRA) and venography (MRV) MRA MRV • Allows studying the macro-vasculature of the brain • Various techniques available

• Indication: – Vascular disorders: stroke, malformations, post- traumatic, vasculitis, …

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Cerebrospinal Fluid (CSF) MRA Flow Imaging

Study of the direction, amplitude and pulsatility of CSF flow

Systole Diastole • Blood  into cranial vault • Blood  out of cranial vault • CSF  spinal canal • CSF  back into cranial vault

Moyamoya syndrome in neurofibromatosis type 1 Bidirectional CSF flow

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6 CSF Flow Imaging CSF Flow Imaging

Magnitude images Phase images • Indication: – CSF flow study: • Craniovertebral junction: Chiari malformations • Sylvian aqueduct • Patency of a third ventriculostomy

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CSF Flow Imaging Diffusion-weighted imaging (DWI)

• Differences in diffusion properties of protons (H+)

• Degree of diffusion depends on: – Physiological micro-structural properties of tissue – Pathological changes of tissue

Chiari 1 malformation

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DWI DWI  ADC

White matter = less degree of CSF = high degree of mobility mobility • ADC = apparent diffusion coefficient • Values, calculated by post-processing

• Advantage compared to DWI: – Represents only local diffusion without contamination by other physical phenomenon such as T2 relaxation

Diffusion CSF > brain tissue ©AP ©AP

7 DWI  ADC DWI  ADC

DWI

DWI ADC

High diffusion Dark Bright

ADC Low diffusion Bright Dark

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Pathological diffusion characteristics DWI / ADC

Restricted diffusion Increased diffusion • Indication: • Represents cytotoxic edema • Represents vasogenic edema – Ischemic injury • = low diffusion • = high diffusion • DWI = bright • DWI = dark – Inflammatory process • ADC = dark • ADC = bright – Infection – Brain tumor – Metabolic disorder T2 DWI ADC

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DWI / ADC DWI / ADC

DWI ADC DWI ADC

Acute hypoxic-ischemic encephalopathy

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8 DWI / ADC Diffusion tensor imaging (DTI)

Characterization of 3D shape of diffusion

• Diffusion = in all • Diffusion ≠ in all directions: isotropic directions: anisotropic

Brain abscess

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DTI DTI z λ1

λ2 • Fractional anisotropy (FA) y = proportion of anisotropic diffusion FA x relative to total diffusion λ 3 • Values range: 0 - 1 Measure diffusion along Calculate shape of various directions (> 6) the ellipsoid

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DTI DTI

• Principal diffusion/fiber direction can be color coded: – Red: right  left – Green: anterior  posterior – Blue: superior  inferior

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9 DTI: qualitative evaluation DTI: qualitative evaluation

Joubert syndrome Control

Old right MCA stroke ©AP ©AP

DTI: qualitative evaluation Fiber tractography (FT)

• FT = complex post-processing technique enables Joubert syndrome Control the reconstruction of the course of major fibers within the brain

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FT application FT application

Joubert syndrome Control

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10 FT application 1H-Magnetic resonance spectroscopy (MRS)

• Allows studying brain metabolites qualitatively and quantitatively

NAA Cr Cho mI

Aberrant course of the right corticospinal tract

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1H-MRS 1H-MRS

Metabolite Significance Patient Control • N-Acetylaspartate (NAA, 2.0 • Neuronal marker ppm) • Glutamate/-mine (2.3 ppm) • Neurotransmitter NAA • Creatine (3.0 ppm) • Energy metabolism Cr • Choline (3.2 ppm) • Cell membrane ”turnover“ Cho • Patient • Myo-Inositol (3.5 ppm) • Osmoregulation mI

• Lactate (1.33 ppm) • Anaerobic glycolysis

Creatine deficiency syndrome

1H-MRS 1H-MRS

Patient Control Patient Control

NAA NAA Cr Cr Cho Cho mI mI Lactate

11 Perfusion-weighted imaging (PWI) Dynamic contrast susceptibility PWI

• Maps the micro-perfusion of the brain tissue • Two techniques: – Dynamic first pass contrast enhanced magnetic susceptibility imaging

– Arterial spin labeling (ASL)

CBV!!

Arterial spin labeling Arterial spin labeling

• Non-invasive hemodynamic imaging • Can be repeated as often as necessary • No IV contrast, radiofrequency labelling • Absolute quantification • Selective vascular territory studies

CBF!!

PWI PWI Clinical applications

• Indication: – Stroke: identification of regions of critical perfusion (PWI-DWI=tissue risk of infarction) – Tumors: high-perfusion = high-grade – Hypoxic-ischemic injury 1-day-old male (39 weeks of gestation) – … with acute neonatal stroke

12 Susceptibility weighted imaging (SWI) SWI

• MRI technique accentuating magnetic properties of blood, blood products, non-heme iron, and calcifications • Difference in the magnetic properties of oxygenated and deoxygenated hemoglobin  phase difference between regions with various concentrations of oxygen

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SWI SWI: application

• Blood, blood products: – Hemorrhagic disorders, stroke, traumatic brain injury, brain tumors, vascular malformation • Calcifications: – Infections, brain tumors, metabolic/ neurodegenerative disorders • Non-heme iron: – Neurometabolic/neurodegenerative disorders

SWI: application SWI: application

Traumatic brain injury (DAI) Sturge-Weber syndrome

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13 Imaging of the spinal cord

• Nervous system includes not only the brain, but also:

– Spinal cord

– Peripheral nerves

– Muscles

Imaging of the spinal cord Imaging of the peripheral nerves

Imaging of the muscles Imaging of the muscles

Courtesy of Dr. A. Klein Courtesy of Dr. A. Klein

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14 Imaging of the muscles Imaging of the muscles

Conclusion Take home messages 1

• Multimodality diagnostic imaging 1. Speak to neuroradiologists to insure that the right sequences are obtained to answer your questions – Anatomical imaging: T1, T2, FLAIR, … 2. In specific clinical situations - certain sequences are key to 1 – Functional imaging: DWI, DTI, H-MRS, … diagnosis: • White matter disorders = T2 + FLAIR • Cerebellar atrophy = coronal T2 • Calcifications/blood in consideration = SWI • Metabolic disorder in consideration = 1H-MRS • Acute neurology = DWI • Inflammation, infections, tumors = T1+contrast 3. Possible artifacts of imaging should always be considered in image interpretation

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Take home messages 2

4. Always look at ventricular size and shape carefully 5. Brain maturation during the first 18-24 months of life are reflected in changes in brain myelination on MRI 6. As a generalization: • T1 weighted images = anatomic considerations • FLAIR and T2 = pathology 7. Use a neuroimaging based pattern-recognition if possible: • White matter disorders • Cerebellar atrophy • Calcifications