Outline
Functional Neuroanatomy
Neuroanatomy overview
Selected functional neuroanatomy
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z
z
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Language
Motor
Vision
Memory/limbic
Functional neuroanatomy and radiotherapy:
selected case studies and imaging pitfalls
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Ronald L. Wolf, M.D., Ph.D.
University of Pennsylvania Medical Center
Major Brain Subdivisions
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Hindbrain
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z
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Brainstem
Cerebellum
Forebrain
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z
Diencephalon
Telencephalon
Midbrain
Optic Chiasm
MBs
SN
OT
RN
SCPs
Pons
Medulla
CN V
CN XII
MCP
V
Cord, Optic Chiasm, Brainstem
Hypertrophic Olivary Degeneration
Level 1
Injury in triangle of Guillain and Mollaret
Cord: weakness/paresis, sensory disruption
Optic chiasm: blindness, field cut
Pons, medulla, midbrain
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z
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z
Ipsilateral cranial nerve(s), contralateral body
Disruption afferents, efferents, circuits
Ataxia, tremor, swallowing, breathing, etc.
Small lesions can cause big problems
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z
Wallenberg – N/V, vertigo, swallowing d/o
Paramedian midbrain/thalamic infarcts - Akinetic mutism
Goyal et al, AJNR 2000; 21: 1073
Paramedian Midbrain/Thalamic Infarcts
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CN III palsy
Lethargic, minimally
arousable
R > L side weakness
Memory impairment
Cerebellum
Primary Fissure
Flocculus
AL
4V
PL
T
Nodulus
Tonsil
4V
Uvula (vermis
), Nodulus
(vermis),
Cerebellum
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Ataxia, abnormalities in tone, equilibrium
and speech
Cerebellar hemispheres - ipsilateral ataxia,
intention tremor, dysmetria, hypotonia,
dysdiadochokinesia, nystagmas
Vermis, flocculus – truncal ataxia
Optic Nerves, Retina, Lacrimal Glands
Level 2
Cochlea
Major Brain Subdivisions
Level 2
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Hindbrain
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z
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Forebrain
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z
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Neurosarcoid:
Neurosarcoid: Hypothalamic
Involvement
HypothalamicHypothalamic-Pituitary Dysfunction
Other Diencephalic Structures
Hypothalamic-neurohypophysial damage
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Diabetes insipidus
Hypopituitarism
Nonhypophysial structure damage
z
Disruption of autonomic functions like
temperature regulation, eating, sleeping,
emotion, and memory
Thalamus
z
Hypothalamic-infundibular-portal damage
z
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Diencephalon
Telencephalon
Hypothalamus and Pituitary
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Brainstem
Cerebellum
Many possible disorders, eg, thermal or
proprioceptive, hemiataxia, involuntary movements,
pain syndromes
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Subthalamic nucleus and globus pallidus
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Metathalamus (LGN, MGN)
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Epithalamus
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z
z
Hemiballismus
Unilateral LGN lesion – field cut
Pineal, chroid plexus, stria medullaris, habenular
nuclei
Telencephalon
Thalamus
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Cortical
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z
z
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Subcortical nuclei
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T
T
STN
T
•
z
RN
Hippocampus
Amygdala, striatum (caudate nucleus, putamen, n.
accumbens), septal nuclei, claustrum
Important telencephalic/diencephalic interactions
z
SN
Paleocortex – olfactory structures
Archicortex – hippocampus, dentate gyrus, etc.
Neocortex – most of the cortex in major lobes
Basal ganglia: striatum + globus pallidus (dienceph.)
Limbic system: hippocampus, cingulate gyrus, septal
nuclei, etc. + hypothalamus, ant. thalamic nucleus, etc.
(dienceph.)
Hippocampus (Coronal, Right)
a: amygdala
b: hipp. body
h: hipp. head
s: subiculum
u: uncal part
arrowhead:
hipp. sulcus
Hippocampus: Selective Vulnerability
CO Poisoning
FLAIR
DWI
Telencephalon:
Telencephalon: Major Cerebral Lobes
e-Anatomy, Micheau A, Hoa D, www.imaios.com
Telencephalon:
Telencephalon: Nuclei
Telencephalon:
Telencephalon: Nuclei
NA
C
GP
P
claustrum
C
C
P
P
GP
GP
C
GP
T1WT1W-IR
P
claustrum
NA
PDW
Brain MRI for Neoplasm
Outline
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Overview basic neuroanatomy
Focus on selected functional neuroanatomy
z
z
z
z
•
Motor
Language
Vision
Memory/limbic
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Functional neuroanatomy and radiotherapy:
selected case studies and imaging pitfalls
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Detection, location, F/U
Navigation
Functional anatomy,
eloquent tissue
Hemorrhage
Cellularity
Angiogenesis
z Vascularity
z Vascular integrity
Metabolism
Biochemical pathways
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T2, DWI, FLAIR, pre/post T1
3D T1, hires FLAIR or T2
fMRI, diffusion tensor
imaging (DTI), MEG
GRE, SWI
Diffusion imaging (DWI, DTI)
Perfusion imaging
z Blood flow, volume (DSC)
z Permeability (DCE)
Spectroscopy
Molecular imaging
Sensorimotor Cortex
Voluntary movements
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Primary motor –
precentral gyrus (area 4)
Participating
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z
z
Supplemental motor area
(SMA, area 6)
Premotor – precentral
gyrus (area 6)
Somatosensory - parietal
cortex (area 5)
SMA
PaCL
Glioma in SMA
Sup. frontal s.
Precentral s.
Central s.
Corticospinal Tract (CST)
Corticospinal Tract: DTI Tractography
Courtesy Paolo Nucifora, MD, PhD, HUP
CST: Wallerian Degeneration
DTI: Displaced CST
Oligoastrocytoma,
Oligoastrocytoma, WHO II/IV
Control Circuits
Primary Sensory
Dorsal column – medial lemniscus
(vibration, proprioception)
proprioception)
Spinothalamic
(pain, temperature)
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Components
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z
z
z
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Main circuit: neocortex > striatum > VAN, VLN
thalamus > premotor and motor cortex
Accessory
z
z
z
Control Circuits
Striatum
Globus pallidus (GP)
Subthalamic nucleus (STN) and substantial nigra (SN)
Red nucleus, lateral vestibular nucleus, thalamic nuclei
(1) striatum > GP > thalamus > striatum
(2) GP > STN > GP
(3) striatum > SN > striatum
DBS Placement in Subthalamic Nucleus
Patterned Finger Tapping
Sensorimotor cortex and control circuits
Language
Repeating written (or spoken) word, WernickeWernicke-Geschwind model
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Right handed
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Non-Right handed
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Primary sensorimotor cortex
SMA
Putamen
Thalamus
Bilateral cerebellum
>95% L dominant
60-65% L dominant
15-20% R dominant
Rest bilateral
Non-dominant
hemisphere has
language functions
Language – Practical
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z
z
z
Broca’s area
Wernicke’s area
Inferior parietal lobule
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z
z
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Neuroanatomy and Eloquence
Perisylvian areas
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Supramarginal and
angular gyri
Associative or
processing area
Auditory, visual,
somatosensory input
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z
SLF/AF connecting
Additional areas
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z
Interindividual anatomic variations, mass
effect, infiltration and reorganization
Functional eloquence unpredictable based on
anatomical features alone
Individualized functional maps and treatment
plans using techniques like fMRI, DTI, and/or
MEG in addition to structural imaging
SMA
Head of caudate nucleus
Pouratian and Bookheimer, Neurosurg Focus 2010
Ojemann et al, J Neurosurg 1989; 71: 316-326
Broca’
Broca’s Area
fMRI:
fMRI: Perisylvian Neoplasm
Infiltrating recurrent glioma
Rhyming, word generation, and sentence completion tasks
FLAIR
T1
T1
Combined fMRI and DTI
Superior Longitudinal/Arcuate
Longitudinal/Arcuate Fasciculus
fMRI:
fMRI:
Bilateral finger
tapping
Tractography:
Tractography:
1. Cortical spinal tracts
2. SLF/arcuate
SLF/arcuate
fasciculus
T2
Vision
fMRI:
fMRI: Visual (Checkerboard)
Parietal occipital sulcus (POS)
POS (crosshairs)
CS (arrowheads)
Calcarine sulcus (CS)
Optic Radiations
Optic Radiations
LGN
LGN
Optic
Raditions
LGN
Optic
Raditions
Optic
Raditions
Optic
Raditions
Optic
Raditions
LGN
Optic Tracts
Optic
Raditions
Memory and Limbic System
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Cortical
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Subcortical
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Yoneoka AJNR 2004; 25: 964
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Septal nuclei
Preoptic area
Hypothalamic nuclei and
mammillary bodies
Anterior thalamic nucleus
Midbrain nuclei
Tracts/connections
z
z
z
Hofer et al,
al, FNANA 2010;4:1
Amygdala, olfactory connections
Hippocampus, dentate gyrus,
subiculum
Parahippocampal gyrus
Cingulate gyrus
Fornix
Mammillothalamic tract
Stria medullaris, terminalis
Limbic System
Limbic System
Amygdala,
Amygdala, hippocampus: left cortical dysplasia,
dysplasia, MB atrophy
Mammillary bodies (MB), mammillothalamic tract (MT), fornix (F)
MB
F
F
MT tract
AC
F
F
Amygdala
Pes hippocampus
Mid hippocampus
Limbic System
Function and Injuries
Septal nuclei (arrowhead), nucleus accumbens (NA), cingulate gyrus
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Cingulate gyrus.
gyrus.
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Emotional reactions – anger, fear, desire
Homeostasis, self preservation
Memory and learning
AC
NA
MB
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z
Limbic Encephalitis: HSV
Wernicke-Korsakoff syndrome
TLE
Wernicke Encephalopathy
fMRI Prediction of Memory Outcome
after Surgery for TLE
Injury to which may impair memory?
A.
L TLE
GOOD OUTCOME
B.
BAD OUTCOME
C.
D.
R TLE
E.
Hippocampus
Fornices, mammillary bodies,
mamillothalamic tracts
Septal nuclei
Caudate nucleus
All of the above
Mesial temporal memory activation detected by fMRI during complex
visual scene encoding correlates with postsurgical memory outcome
Motor Mapping: Finger Tapping
Outline
•
•
Overview basic neuroanatomy
Focus on selected functional neuroanatomy
z
z
z
z
•
LUE deficit after resection, fMRI and intraop mapping
Motor
Language
Vision
Memory/limbic
Functional neuroanatomy and radiotherapy:
selected case studies and imaging pitfalls
z
Motor and Language
Central sulcus
Hand and Face Motor Mapping
fMRI:
fMRI: GB Distorting Anatomy
Atypical ganglioglioma progressing after incomplete resection
T1W
FLAIR
fMRI: Face (G), Hand (R), Foot (B) motor mapping
DTI: CST (G), AF (Y)
RTOG Grade 4 Toxicity S/P GK
Sept.
Oct.
Infiltrating Glioma
Dec.
fMRI: Foot (Red), Hand (Blue) motor mapping
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GK in Oct.
(before middle
scan)
Status
epilepticus
soon after
For the targeted volume, which is true?
Surg Path: Astrocytoma WHO II
0 mo.
2 mo. (SIM)
3 mo.
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A.
Targeted volume
B.
C.
D.
E.
Resection will not be a problem,
no motor activation close enough
fMRI is irrelevant, the anatomy is
clear on the structural images
Patient will be weak but will likely
recover
Patient will be permanently weak
Language deficits are unlikely
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After SIM:
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Decision
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Focal therapy?
59 Gy
Chemo
Considerations for Clinical fMRI
STG
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Significance of activation (or lack of activation)
z
Bx site
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Sentence completion
54 Gy
No chemo
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z
“Inoperable”
Inoperable” GBM: Language Mapping
Passive listening
Initial
Can fMRI determine if an activated lesion is critical
(or if a non-activating region is not critical)?
Relationship of statistical test “significance” to
neuronal function?
Patients and pathology
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z
z
Task performance altered by pathologic function like
aphasia, or simply vision or hearing impairment
Pathophysiology alters activation-flow coupling –
AVM alters flow, hemosiderin destroys signal
Task relevance to function in location of lesion
Diffuse Infiltration
Premotor LGG
Surgical vs. radiation plan
Speech arrest adjacent to glioma
Right handed: Broca’
Broca’s Area Uncertain
Significance of Poor or No Activation?
No speech arrest adjacent to oligoastrocytoma (WHO II)
Early case: Aphasic after resection LGG, rightright-handed patient
Verbal Fluency
Bilateral Motor
Right handed: Progressive
Astrocytoma (WHO III)
February 2008 – initial preop
December 2010 - progression
In this right handed patient, which of
the following is true?
A.
B.
C.
D.
E.
fMRI indicates reorganization of
language to right hemisphere
Pathology may create false negative
left frontal activation
The right hemisphere in general has
no role in language
If left handed, I wouldn’t be worried
No problem articulating preference
for Beatles over Stones
False Negative Potential
Cavernoma
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Preop
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Caudate has role in
memory and
language
Appropriate task?
Lack of activation
near cavernoma not
useful
Postop infarct - aphasic
No Activation ≠ No Function
7y, Male AVM
AVM, 7 YM
Cavernoma
SWI mIP
Courtesy Erin Simon Schwartz, MD, CHOP
Motor fMRI,
fMRI, RD2: No Activation
MEG: Motor Beta Band
LD2
Courtesy Erin Simon Schwartz, MD, CHOP
RD2
Courtesy Erin Simon Schwartz, MD, CHOP
Summary
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Basic neuroanatomy already included in
planning
More detailed neuroanatomic knowledge
increasingly important with radiosurgery and
proton therapy
Conventional anatomic imaging not sufficient
due to individual variation, pathology,
distortion, etc.
Mapping techniques like fMRI, DTI, MEG needed
T1 Atlas Stacks
Acknowledgements
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Gul Moonis, Beth Israel Deaconess
Joe Maldjian, Wake Forest
Erin Simon Schwartz, CHOP
Selected images created using Cerefy
Neuroradiology Atlas (www.cerefy.com)
Selected images from references cited in
talk
Atlas Overlays