Download Multimodality Imaging - The Sackler Institutes

Multimodality Imaging
(MRI, PET, CT, etc..)
Jonathan Dyke, Ph.D.
Assistant Research Professor
of Physics in Radiology
Citigroup Biomedical Imaging Center
Weill Cornell Medical College
Sackler Institute for Developmental Psychobiology
Summer Lecture Series
July 9, 2009
Cyclotron
Radiochemistry
Cyclotron design from Ernest Lawrence’s
1934 patent application.
Basic HS Chemistry is useful.
What does the atomic # define?
Atomic # = # protons (never changes)
What does the atomic mass define?
#protons + #neutrons = Mass #
Radioisotope Production
Production of
18F
precursor to FDG
Target Material: Purified Water
16O
8
+ p ->
18F
9
+n
Positron Emission Tomography
“PET” Scan (“DOG” Scan)
Is a positron stuff of fiction?
e+ + e- -> ga + gb
PET: Coincidence Detection
Courtesy: Brookhaven National Lab
Filtered Back Projection
(Key for both PET and CT!)
Courtesy: Univ British Columbia
Clinical Applications of PET
Alzheimer’s Disease
Primate - 11C-Raclopride Imaging
Courtesy: Shankar Vallabhajosula, Ph.D.
18F-FDG
Lymphoma Study:
2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG)
11C-5-Hydroxytryptophan
(5-HTP)
Image Analysis:
Standard Uptake Value:
Pre-Tx SUV=15 Post-Tx SUV=2
Courtesy: PET/CT in clinical practice By T. B. Lynch, James Clarke
Computed
Tomography
“CAT Scan”
Creation of X-Rays
Circa 1896
X-Ray Tube Construction
Circa 1900
Circa 2000
X-Ray Densities
Do the following appear
Dark or light on an X-Ray image?
•Air
•Fat
•Bone
CT Hounsfield Units
CT Hardware
Advantages:
1) CT completely eliminates the superimposition of images of
structures outside the area of interest.
2) because of the inherent high-contrast resolution of CT,
differences between tissues that differ in physical density
by less than 1% can be distinguished.
3) data from a single CT imaging procedure consisting of either
multiple contiguous or one helical scan can be viewed as
images in the axial, coronal, or sagittal planes, depending on
the diagnostic task. This is referred to as multiplanar
reformatted imaging.
In the ED it’s FAST!
CT Diagnostic Utility:
Head: Trauma, Stroke, Tumor, Biopsy
Chest: Lungs, Pneumonia, Emphysema, Embolism
Cardiac: Coronary artery disease (High Dose)
Abdominal and pelvic:
Renal stones, appendicitis, pancreatitis, diverticulitis
Extremities: Fractures, dislocations.
CT - Stroke
CT Perfusion
CBF
CBV
MTT
AJNR 2000;21:1441–1449.
CT Radiation Dose
Diagnostic Advantage
Vs.
Increased Risk Cancer
Assumes linear relationship between radiation dose
and cancer risk (Controversial).
Risk for pediatric patients developing cancer
from CT scan is greater than adults.
~ 500 in every 600,000 scans.
“CT is an extremely valuable tool, and nobody should
hesitate to undergo CT when it is indicated.”
Advanced
MRI Applications
•CONTRAST ENHANCEMENT
•DIFFUSION IMAGING
•FAST IMAGING METHODS
•FUNCTIONAL IMAGING
•PERFUSION IMAGING
•SPECTROSCOPY
MRI CONTRAST
ENHANCEMENT
Magnetism of Materials
Dia
Para
Ferro
Super
Weakest
Weak
Strong
Strong
c~-1
c~10
c~25,000
c~5000
How does it affect the signal?
•What type of material is Gadolinium?
•How many unpaired e- does in Gd-DTPA?
•What compound do we detect the
effect of contrast on?
Contrast Mechanisms Dictate Method of Study
in Magnetic Resonance Imaging
How does an agent affect relaxation times?
1
T1,2
=
1
T10,20
+ R1,2 C
Solomon-Bloembergen Equations (1955)
What factors influence whether the T1 or T2
effect will dominate the MRI signal?
0.7
0.6
0.5
% Signal Increase
0.4
0.3
Whole Brain
0.2
Muscle/Vessel
0.1
0
-0.1
0
0.5
1
1.5
2
2.5
-0.2
-0.3
-0.4
Tim e (Minutes)
3
3.5
4
4.5
5
Clinical Apps:
Why are contrast agents necessary
given the excellent resolution of
un-enhanced MRI images?
When is a contrast scan prescribed?
Tumor, Stroke, Angiography
CNS disease
But.. Talk is cheap..
Nephrogenic Systemic
Fibrosis
MRI
DIFFUSION
IMAGING
BASIC DWI PHYSICS
CLINICAL APPLICATIONS
TRACTOGRAPHY
What physical aspects or systems
In nature exhibit diffusion?
What principles govern diffusion?
The “Drunken” Walk
Einstein – 1905
How far does a drunk walk?
<R(t)2>= 2 D t vs. R(t)= v t
-3
3x10
2
mm /s
D H O=
2
Dbrain = 1x10-3 mm2/s
What affect does diffusion
have on the MRI signal?
S=S0 e
–b D
DWI Atten Brain = 1/(2.782)
DWI Atten CSF = 1/(2.782^3)
How can you image diffusion
at the cellular level accounting
for patient motion?
Patient motion ~ 1-2mm
Diffusion length ~ 10-100mm
Pulse Sequence: Spin-Echo Diffusion Weighting
180o
90o
RF
Excitation G
G
Gx
Image
Gy
Gz
Acquisition
Why the different contrast
between a DWI & ADC image?
DWI = ADC
Clinical Apps:
Acute AML pre/post Tx
*Courtesy: Doug Ballon, 2003
Isotropic vs. Anisotropic
A.W. Song, http://www.biac.duke.edu/education/courses/fall04/fmri/
Diffusion Tensor Imaging
3T MRI – NYP - Tumor
MR
FUNCTIONAL
IMAGING
BOLD EFFECT PHYSICS
PHYSIOLOGICAL FACTORS
CLINICAL APPLICATIONS
Roy, C.S., and Sherrington, C.S. 1890.
On the regulation of the blood supply
of the brain. J. Physiol. 11:85-108.
100 years pass…..
Ogawa, S., Lee, T.M., Nayak, A.S., and
Glynn, P. 1990. Oxygenation-sensitive
contrast I magnetic resonance image of
rodent brain at high magnetic fields.
Magn. Reson. Med. 14:68-78.
How does BOLD really work?
•Oxyhemoglobin is diamagnetic
•Deoxyhemoglobin is paramagnetic
•Neuronal activity->Less deoxyhemoglobin
•Less susceptibility difference between
capillary vessel and brain tissue
•Longer T2*
•Signal increase in T2* Sequence
How big an increase are we talking about?
Blood Oxygen Level
Dependent Signal
Source: Buxton book Ch 17
Hemodynamic Response
Dale & Buckner, 1997
Repeated Trials –
Dale/Buckner 1997
Motor Activation in AFNI
Where do we expect activation?
Cortical mapping in the
surgical suite.
Neuron, 2006,18;643-653. – Courtesy BJ Casey
Clinical Apps:
• Improving clinical procedures, e.g.
presurgical planning for brain tumors
•
•
•
•
• Direct: Mapping of functional properties of
adjacent tissue
• Indirect: Understanding of likely
consequences of a treatment
Understanding cognition
Studying brain development
Investigating brain physiology
** Henning – Minimally Conscious State
MR PERFUSION
IMAGING
Physiologically, what happens when
a tracer enters the blood supply?
•What factors influence the
distribution and kinetics?
Johns Hopkins – Dept Radiology
T1W – DCE MRI
DYNAMIC CONTRAST
ENHANCED IMAGING
2D Fast Spoiled Gradient Echo, 12 mm slice, 8/0 slices, TR/TE 8 ms/2 ms,
15.63 kHz RBW, 22 cm FOV, 256 x 128 matrix, 8.56 sec/resolution
Pediatric Osteogenic Sarcoma: Post-Chemotherapy
Grade IV Responder: 100% Necrotic
4
2
1
3
S/S0
2.25
2
2
1.75
4
1.5
1
1.25
3
1
0.75
0
1
2
3
Minutes
4
5
DCE-MRI & ANGIOGENESIS
•What role does neovasculature fill in
tumor growth? (Goldman,1907)
•How far from a vessel can a tumor cell
survive? (Thomlinson & Gray,1955)
•Does DCE produce any physiologically
significant parameters?
Pharmacokinetic Modeling of Tracer Kinetics
(Kety, 1951)
ve dCe(t) = Ktrans (Cp(t)-Ce(t))
dt
Cp
Cp
Brix/Hoffman 2 Compartment Model
Gd-DTPA 0.1 mM/kg
Kin
Intravascular
Plasma
k12
kep
Interstitial
Lesion
kel
Does this model actually fit real data?
Compartmental Model Fits
0.8
0.7
Grade II - 50% Necrotic:
A=0.75, kep=5.47/min, kel=0.03/min
S(t)/S0-1
0.6
0.5
0.4
0.3
Grade IV - 100% Necrotic:
A=0.30, kep=2.79/min, kel=-0.21/min
0.2
0.1
0
0
0.5
1
1.5
Time (Minutes)
2
2.5
3
CLINICAL APPS:
•Tumors: breast, brain, bone
•Drug Trials: anti-angiogenic
•Arthritis: joint/synovium
•BBB leakage/permeability
T2*W – DSC MRI
DYNAMIC SUSCEPTIBILITY
CONTRAST
Representative Perfusion Maps
CBV
MTT
CBF
EPI
62 year old with left MCA territorial stroke. The perfusion maps
show prolonged MTT with corresponding decreased CBF and CBV.
“Arterial Input Function”
-ln(S/S0)
Raw SI
Minutes
Minutes
“CT Perfusion is for wimps.”
Difficulties in MRP quantitation.
•Delay
•Dispersion
•Saturation Effects
•Partial Volume Effects
•Susceptibility Masking
•Conversion to Concentration
Refs: van Osch,2000; Rausch,2001; Wu,2003
Cerebral Blood Volume
1  hLV 1
CBV 
1  hSV 
 C (t )dt
 AIF (t )dt
t
Cerebral Blood Flow
Ct (t )  CBF  AIF (t )  R(t )
Mean Transit Time
MTT=CBV/CBF
Central Volume Theorem
CBV
(ml/100 gm )
Normal GM = 4.4%+/-0.9
Normal WM = 2.3%+/-0.4
Ischemia = >6 ml
CBF
(ml/100 gm/min)
Normal GM = 39+/-10.3
Normal WM = 14.7+/-4.1
Ischemia < 10.0
DWI/PWI Services in Stroke: www.synarc.com
MR SPECTROSCOPY
NMR Active Nuclei
What can we see?
Raw Signal
“FID”
FFT
“Chemical Shift”
Electron Shielding
Water = 4.7ppm
Lipid = 1.3 ppm
Dn =(4.7-1.3) ppm*127.5MHz
= 434 Hz @ 3.0 Tesla
T=1/n = 2.3 ms (IP, OOP)
1H
Metabolites
NAA
CHO
CRE
LAC
A sampling of
Lac 3
Para-PyruvateCH3
Alanine 3
Arginine 4
Lys 5
Leu 3
Leu 4
g-aminobutyric acid 3
Lys 3
Acetate 2
Arginine 3
Ile 3
Pro 4
N-Acetyl CH3
N-Acetyl CH3
Glu 3
N-Acetyl CH3
Met S(CH3)
Met 3
Gln 3
GSH Glu 3
GSSG Glu 3
NAAG Glu 4
2-Hydroxy-Glutarat
Val 3
g-aminobutyric acid 2
Glu 4
Pyr 4
Succinate
Carnitine 2
2-Keto-Glutarat
Gln 4
Citrate
B-Alanine 2
GSSG Glu 4
GSH Glu 4
Citrate
1.32
1.36
1.47
1.64
1.7
1.71
1.71
1.89
1.89
1.91
1.92
1.97
1.99
2.01
2.05
2.06
2.07
2.13
2.14
2.15
2.17
2.17
2.21
2.27
2.27
2.3
2.34
2.4
2.4
2.45
2.46
2.46
2.52
2.55
2.55
2.57
2.62
1.33 doublet
1.44 doublet
1.69 multiplet
1.71 multiplet
1.91 multiplet
1.92 singlet
1.96 multiplet
2.08 multiplet
2.16 singlet
2.14 singlet
2.16 multiplet
2.14 multiplet glutamate
2.24 multiplet
2.36 multiplet gultamate
2.41 multiplet
doublet
doublet
1H
metabolites
g-aminobutyric acid 4
3.02
2-Keto-Glutarat
3.03
Creatine CH3
3.03
PCreatine CH3
3.03
Cn CH3
3.07
phosphoethanolamine
3.15
B-Alanine 3
3.18
choline
3.2
Arginine 5
3.21
N(CH3)3
3.21
PE (N)
3.21
Cysteamine (N)
3.23
phospho-choline
3.24
Carnitine (CH3)
3.24
Glc 2B
3.25
Oxal-Acetate
3.25
Tau (N)
3.25
Para-Pyruvate CH2
3.27
Phe 3
3.27
phosphatidylcholine
3.28
glycerophospho ethanolamine3.29
(N)
Inositol (myo) 5
3.29
Hypotau (S)
3.36
Inositol (scyllo)
3.36
Pro 5
3.39
Glc 4a
3.41
Glc 4B
3.41
Tau (S)
3.41
Glycogen 4
3.43
Glc 5B
3.44
Carnitine 4
3.45
Glc 3B
3.5
Glc 2a
3.55
Inositol (myo) 1,3
3.55
Gly 2
3.56
Thr 2
3.58
PC (N)
3.59
Inositol (myo) 4,6
3.61
3.04 singlet
singlet
singlet
3.26 triplet
singlet
3.28 triplet
3.40 triplet
3.42 triplet
3.46 triplet
3.47 ddd
3.54 dd
3.56 doublet of doublets
3.61 singlet
3.63 dd
Ex-vivo Mouse brain perchloric acid extract @ 11.4T
What price is paid in detecting these signals?
Grade III
GBM
Pre-Tx
Dyke JP, Sanelli PC, Voss HU, Serventi JV, Stieg PE, Schwartz TH, Ballon D,
Shungu DC, Pannullo SC. Monitoring the Effects of BCNU Chemotherapy
Wafers (Gliadel®) in Glioblastoma Multiforme with Proton Magnetic Resonance
Spectroscopic Imaging at 3.0 Tesla. J Neurooncol. 2007 Mar;82(1):103-10.
31P
Metabolites
@ 3.0 Tesla