Functional neuroimaging.pptx

1. Dr. Sunil Kumar Sharma
Senior Resident
Dept. of Neurology
GMC Kota

2. FUNCTIONAL NEUROIMAGING
 Functional neuroimaging is visualization of brain
functions, most notably cerebral blood flow, glucose
metabolism, receptor binding, and pathological
depositions.
 Functional neuroimaging is particularly valuable for
mapping brain functions or depicting disease-related
molecular changes that occur independently of or
before structural changes.

3.  Regarding applications of PET and SPECT, the focus
will be on investigations of cerebral blood flow (CBF)
and glucose metabolism in-
-Dementia,
-Parkinsonism,
-Brain tumors,
-Epilepsy.
 Localization of brain function may be the main focus of
fMRI research at present and is increasingly utilized in
presurgical mapping.

4. FUNCTIONAL NEUROIMAGING MODALITIES
 fMRI
 PET
 SPECT

5. Functional Magnetic Resonance
Imaging(fMRI)
 It relates to the blood oxygen level-dependent (BOLD)
effect, which is due to a transient and local access of
oxygenated blood, resulting from changes in regional
CBF and neuronal activity.
 Shows images of changing blood flow in the brain
associated with neural activity
 Reflects which brain structures are activated during
performance of different tasks.

6. fMRI…
 The subject is required to carry out some task
consisting of periods of activity and periods of rest.
 Experimental stimuli (e.g., words that must be read)
are presented either in a block design (series of words
for 20–30 seconds alternating by rest blocks of similar
length, over several minutes) .

7. fMRI…
 During the activity, the MR signal from the region of
the brain involved in the task normally increases due to
the flow of oxygenated blood into that region
 During an fMRI experiment, the brain of the subject is
scanned repeatedly, using the echo planar imaging
(EPI).
 Signal processing is then used to reveal these regions.

8. fMRI…
 The image shows areas active for visual memory
(green), aural memory (red), and both types of
memory (yellow).

9. fMRI…
Advantages-
 It requires no contrast agent .
 High quality anatomical images can be obtained
in the same session as the functional studies.
 Can be repeated multiple times
Disadvantages-
 Cannot perform receptor-ligand studies like PET and
SPECT
 Extremely sensitive to head movements .
 Loud sound from magnets

10. Contraindications: –
 Irremovable magnetic devices
 Extreme claustrophobia

11. Single Photon Emission Computed
Tomography(SPECT)

12. SPECT Scan
 Single Photon Emission Computed Tomography
 The first SPECT measurements were performed in the
1960s (Kuhl and Edwards, 1964).
 Shows how blood flows through arteries and veins in
the brain
 Can detect reduced blood flow in the brain

13. Single-Photon Emission Computed
Tomography (SPECT)
 SPECT employs gamma-emitting radionuclides that decay
by emitting a single gamma ray.
 Typical radionuclides employed for neurological SPECT are
technetium-99m (99mTc; half-life = 6.02 hours) and iodine-
123 (123I; half-life = 13.2 hours).
 Two most widely used CBF tracers for SPECT are ,
-Hexamethylpropyleneamine oxime [99Tc]HMPAO
-Ethylcysteinate dimer [99Tc]ECD

14. SPECT…
 Gamma cameras are used for SPECT acquisition,
whereby usually two or three detector heads rotate
around the patient’s head to acquire two-dimensional
planar images (projections) of the head from multiple
angles .
 Finally, 3D image data reconstruction is done by
conventional reconstruction algorithms.

15. SPECT Vs PET
 SPECT has considerably lower sensitivity than PET.
 Rapid temporal sampling (image frames of seconds to
minutes) is the strength of PET, SPECT (20 to 30 minutes).
 Furthermore, the spatial resolution of modern SPECT is
only about 7 to 10 mm,(PET 3-5 mm) deteriorating with
increasing distance between object and collimator .
 The important advantages of SPECT over PET are the lower
costs and broad availability of SPECT systems and
radionuclides.

16. SPECT Scan Uses in Neurology
 Pre-surgical evaluations of uncontrolled seizures
 Blood deprived areas of the brain after a stroke
 Dementia

17. SPECT…
Alzheimer’s

18. SPECT…
Transaxial slices of 73-y-old man
with FTD and 2-y history of
progressive short-term memory
loss show marked hypoperfusion
of anterior cingulate gyrus
(arrowhead) and mesial frontal
lobes (arrows).
MRI showed only mild frontal
lobe atrophy, which could not
explain brain SPECT findings.

19. A 62-y-old right-handed,
hypertensive man had stroke
2 y ago and now has severe
memory impairment,
dysarthria, and urinary
incontinence.
Transaxial, sagittal, and
coronal slices show multiple
scattered focal areas of
hypoperfusion involving
entire cerebral cortex, a
pattern frequently found in
vascular dementia.
SPECT…

20. SPECT…
A 21-y-old left-handed man had
history of tonic–clonic seizures since
age 8.
Head CT findings were normal.
MRI showed T2-weighted
hyperintense signal and slightly
decreased size of right hippocampus.
EEG showed acute waves in right
frontal and temporal lobes.
Interictal and ictal transaxial and
coronal slices show hypoperfusion
and hyperperfusion, respectively, of
right temporal lobe (arrows).

21. PET

22. PET…
 The concept of modern PET was developed during the
1970s (Phelps et al., 1975). ]
 The underlying principle of PET, and also of SPECT, is
to image and quantify a physiological function or
molecular target of interest in vivo by noninvasively
assessing the spatial and temporal distribution of the
radiation emitted by an intravenously injected target-
specific probe (radiotracer).

23. PET…
 Importantly, PET and SPECT tracers are administered
in a nonpharmacological dose (micrograms or less).
 Because of their ability to visualize molecular targets
and functions on a macroscopic level with unsurpassed
sensitivity, down to picomolar concentration, PET and
SPECT are also called molecular imaging techniques

24. PET…
 In the case of PET, a positron-emitting radiotracer is
injected.
 The emitted positron travels a short distance in tissue
before it encounters an electron, yielding a pair of two
annihilation photons emitted in opposite directions.
 This photon pair leaving the body is detected within a
few nanoseconds by scintillation detectors of the PET
detector rings that surround the patient’s head.

25. PET…
 Assuming that the annihilation site is located on the line
connecting both detectors (known as the line of response [LOR]),
three-dimensional (3D) PET image data sets of the distribution
of the PET tracer and its target are generated by standard image
reconstruction algorithms.
 The spatial resolution of modern PET systems is about 3 to 5
mm.
 Today’s PET systems are either constructed as hybrid PET/CT or,
more recently, PET/MRI systems.
 Although the clinical utility of the latter still needs to be defined

26. PET…

27. PET…
 Commonly used radionuclides in neurological PET ---
-Carbon-11 (11C, half-life = 20.4 minutes),
-Nitrogen-13 (13N, half-life = 10.0 minutes),
-Oxygen-15 (15O, physical half-life = 2.03 minutes),
-Fluorine-18 (18F, half-life = 109.7 minutes),
Which are all cyclotron products.

28.  Whereas the relatively long half-life of 18F allows
shipping 18F-labeled tracers from a cyclotron site to a
distant PET site, this is not possible in the case of 15O
and 11C.
 Thus, 18F-labeled substitutes are most commonly used

29. Radiotracer used in PET & SPECT

30.  We will primarily focus on PET studies using the
glucose analog, 2-deoxy- 2-(18F)fluoro-d-glucose
([18F]FDG), to assess cerebral glucose metabolism.
 FDG represents an ideal tracer for assessment of
neuronal function and its changes (Sokoloff, 1977).

31.  After uptake in cerebral tissue by specific glucose
transporters, [18F]FDG is phosphorylated by
hexokinase.
 [18F]FDG-6-P is neither transported back out of the
cell nor can it be metabolized further.
 Therefore, the distribution of [18F]FDG in tissue
imaged by PET (started 30–60 minutes after injection
to allow for sufficient uptake; 5- to 20-minute scan
duration) closely reflects the regional distribution of
cerebral glucose metabolism and, thus, neuronal
function

32. (PET) scan used in-
- Alzheimer's disease and other dementias
- Parkinson's disease,
- Multiple sclerosis,
- Transient ischemic attack (TIA),
- Huntington's disease,
- Stroke, and
- Schizophrenia.
- Epilepsy.
(To Remember-PET SCAM)

33. [18F]FDG PET in early Alzheimer disease
Characterized by mild to
moderate hypometabolism of
temporal and parietal cortices
and posterior cingulate gyrus
and precuneus.
Distinct asymmetry is often
noticed.
As disease progresses, frontal
cortices also become involved.
Top, Transaxial PET images of
[18F]FDG uptake
Bottom, Results of voxel-based
statistical analysis using
Neurostat/3D-SSP.

34. [18F]FDG PET in advanced Alzheimer
disease
 Advanced disease stage is characterized by severe
hypometabolism of temporal and parietal cortices and
posterior cingulate gyrus and precuneus. Frontal
cortex is also involved.
 sensorimotor and occipital cortices, basal ganglia,
thalamus, and cerebellum are spared.
 Mesiotemporal hypometabolism is also apparent.

35. [18F]FDG PET in advanced Alzheimer
disease

36. Pittsburgh Compound-B (PIB)
 Radiolabeled thioflavin
derivative
 [N-methyl-(11)C]2-(4’-
methylaminophenyl)-6-
hydroxybenzothiazole
 Selectively binds to amyloid
plaque and cerebrovascular
amyloid
 Significant retention seen in:
 90+% AD patients
 60% patients with MCI
 30% “normal” elderly
 Very short half life: 20
minutes
Amyloid Imaging:
Pittsburgh Compound-B PET
T1W-MRI PIB- PET
ControlAD

37. 18F]FDG PET in the different variants of primary
progressive aphasia (PPA)
 [ [18F]FDG PET scans in logopenic variant PPA (lvPPA)
are characterized by a leftward asymmetric
temporoparietal hypometabolism
 semantic variant PPA (svPPA) involves the most rostral
part of the temporal lobes
 Patients with the nonfluent variant PPA (nfvPPA)
typically show leftward asymmetric frontal
hypometabolism with inferior frontal or posterior
fronto-insular emphasis.

39. [18F]FDG PET in dementia with Lewy bodies
(DLB)
 This disorder affects similar areas as those affected by
Alzheimer disease (AD).
 Occipital cortex is also involved, which may distinguish DLB
from AD.
 Mesiotemporal lobe is relatively spared in DLB.
 A very similar pattern is observed in Parkinson disease with
dementia (PDD).

40. [18F]FDG PET in dementia with Lewy
bodies (DLB)

41. 18F]FDG PET in behavioral variant of
frontotemporal dementia (bvFTD)
 Bifrontal hypometabolism is usually found in FTD in a
somewhat asymmetrical distribution.
 At early stages, frontomesial and frontopolar
involvement is most pronounced, while parietal
cortices can be affected later in disease course.

42. 18F]FDG PET in behavioral variant of
frontotemporal dementia (bvFTD)

43. 18F]-FDOPA PET(L-3,4-Dihydroxy-6-[
18F]fluorophenylalanine)
 PET scans highlight the loss of dopamine storage capacity in
Parkinson’s disease.
 In the scan of a disease-free brain, made with [18F]-FDOPA PET (left
image), the red and yellow areas show the dopamine concentration in a
normal putamen, a part of the mid-brain.
 Compared with that scan, a similar scan of a Parkinson’s patient (right
image) shows a marked dopamine deficiency in the putamen.

44. [18F]FDG PET in Parkinson disease (PD).
 characterized by (relative) striatal hypermetabolism.
 Temporoparietal, occipital, and sometime frontal
hypometabolism can be observed in a significant
fraction of PD patients without apparent cognitive
impairment.
 Cortical hypometabolism can be fairly pronounced,
possibly representing a risk factor for subsequent
development of PDD.

45. [18F]FDG PET in Parkinson disease (PD).

46. [18F]FDG PET in multiple system atrophy (MSA).
 In contrast to Parkinson disease, striatal
hypometabolism is commonly found in MSA,
particularly in those patients with striatonigral
degeneration (SND, or MSA-P).
 In patients with olivopontocerebellar degeneration
(OPCA, or MSA-C), pontine and cerebellar
hypometabolism is particularly evident.

47. [18F]FDG PET in multiple system atrophy
(MSA).

48. [18F]FDG PET in progressive supranuclear
palsy (PSP)
 Typical finding in PSP is bilateral hypometabolism of
mesial and dorsolateral frontal areas (especially
supplementary motor and premotor areas).
 Thalamic and midbrain hypometabolism is usually also
present.
 In line with overlapping pathologies in FTD and PSP,
patients with clinical FTD can show a PSP-like pattern,
and vice versa

49. [18F]FDG PET in progressive supranuclear
palsy (PSP)

50. [18F]FDG PET in corticobasal degeneration
(CBD)
 In line with the clinical
presentation, CBD is
characterized by a strongly
asymmetrical hypometabolism
of frontoparietal areas
(including sensorimotor cortex;
often pronounced parietal),
striatum, and thalamus.

51. [18F]FDG and [18F]FET PET in a left frontal
low-grade oligodendroglioma (WHO grade II).
•[18F]FDG uptake (middle) of low-grade gliomas is usually
comparable to white-matter uptake, prohibiting a clear
delineation of tumor borders.
•In contrast, the majority of low-grade gliomas (particularly
oligodendroglioma) show intense and well-defined uptake
of radioactive amino acids like [18F]FET (right) even
without contrast enhancement on MRI (left).

52. [18F]FDG and [18F]FET PET in a right mesial temporal
high-grade astrocytoma (WHO grade III)
•In contrast to low-grade gliomas, high-grade tumors usually have
[18F]FDG uptake (middle) that is distinctly higher than white
matter and sometimes even above gray matter, as in this case.
•Nevertheless, the [18F]FET scan (right) clearly depicts a rostral
tumor extension that is missed by [18F]FDG PET owing to high
physiological [18F]FDG uptake by adjacent gray matter.
•Tumor delineation is also clearer on [18F]FET PET than on MRI
(left).

53. [18F]FDG and [18F]FET PET in a primary
CNS lymphoma (PCNSL).
•PCNSL usually show a very intense [18F]FDG uptake (middle),
while metabolism of surrounding brain tissue is suppressed
by extensive tumor edema (see MRI, left).
•[18F]FET uptake (right) of cerebral lymphoma can also be
high

54. 18F]FDG and [18F]FET PET in a recurrent high-
grade astrocytoma (WHO grade III)
•[ [18F]FDG uptake (middle) is clearly increased above
expected background in several areas of suspected tumor
recurrence on MRI (left), confirming viable tumor tissue
•In comparison to [18F]FDG PET, [18F]FET PET (right) more
clearly und extensively depicts the area of active tumor.

55. [18F]FDG PET and ictal [99mTc]ECD SPECT
in left frontal lobe epilepsy
 In this patient, MRI scan (top row) was normal, whereas
[18F]FDG PET showed extensive left frontal hypometabolism
(second row).
 Additional ictal and interictal 99mTc]ECD SPECT scans were
performed for accurate localization of seizure onset.
 Result of a SPECT subtraction analysis (ictal—interictal;
blood flow increases above a threshold of 15%, maximum
40%) was overlaid onto MRI .
 [18F]FDG PET scan (third and fourth rows, respectively),
clearly depicting the zone of seizure onset within the
functional deficit zone given by [18F]FDG PET.

56. [18F]FDG PET and ictal [99mTc]ECD SPECT
in left frontal lobe epilepsy

57. [18F]FDG PET in left temporal lobe epilepsy
 Diagnostic benefit of [18F]FDG PET is greatest in patients
with normal MRI in which [18F]FDG PET still detects well-
lateralized temporal lobe hypometabolism(second row: left
temporal lobe hypometabolism).
 As in this patient with left mesial temporal lobe epilepsy,
the area of hypometabolism often extends to the lateral
cortex (functional deficit zone; third row: PET/MRI fusion).
 In meta-analyses, the sensitivity of [18F]FDG PET for focus
lateralization in TLE was reported to be around 86%,
whereas false lateralization to the contralateral side of the
epileptogenic focus rarely occurs (<5%)

58. [18F]FDG PET in left temporal lobe epilepsy

59. Thank You

60. References
 Bradley’s Neurology In Clinical Practice; 7’th Ed.
 Brain SPECT in Neurology and Psychiatry(Edwaldo E.
Camargo)
 Handbook of Functional neuroimaging of cognition;
Roberto Cabeja & Albert Kingstone
 Functional MRI : Methods and Applications; (Stuart Clare
1997)
 Learningradiology.com