A.B.Madhan Kumar Mentor: Dr. Charles M. Laymon Department of Radiology
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Transcript of A.B.Madhan Kumar Mentor: Dr. Charles M. Laymon Department of Radiology
Investigation of low white matter glucose metabolism in Familial
Alzheimer Disease (FAD)
A.B.Madhan Kumar Mentor: Dr. Charles M. Laymon Department of
Radiology University of Pittsburgh Project Aims To learn the
principle and application of various radioligand tracers in AD, FAD
and control subjects To get familiarized with different compartment
models for the radiotracers in the AD, FAD and control subjects
Data analysis of the results from the compartmental model as
applied to FAD and control subjects (FDG as tracer) 18F-FDG for PET
imaging 18F-FDG-P (trapped) hexokinase 18F-FDG
metabolically active cells within a tissue In AD and certain
dementias the18F-FDGuptake by the cells are greatly diminished due
to lower glucose metabolism Red-high FDG uptake blue-low FDG uptake
MRI/PET images forFAD subject h3537 (skull removed)
MRI image FDG-PET image 18F-FDG and 11C-PIB PET imaging
Methodology 18F-FDG half life 110 minutes 11C-PIBhalf life 20
minutes PIB alone or (B) PIB and FDG For investigation in AD, the
subjects are administered with: Sequence of administration: 1.
11C-PIB first 2. 18F-FDG after about 10 half lives of PIB (approx
3-4 h later) Motivation for this study
based on the recent observation that 18F-FDG is accumulatedless in
subcortical white matter region (SWM) in FADsubjects when compared
to control subjects Regional Distribution of FDG uptake in AD, FAD
and control subjects
(Concentration ratio to cerebellum at 60 minutes)(static PET data)
cohens d value -FAD patients (15) Subjects Control (89) Region FAD
&control ACG 0.1958 PAR 0.8081 AVS 0.2947 PRC 0.8049 FRC 0.5621
SWM 1.6085 AD patients (33) effect size FRC ACG PRC AVS LTC PAR MTC
OCC SMC PON SWM Compartments are structureless pools containing the
tracers in distinct state
perfusion phosphorylation Plasma Brain tissue 1818 k1 k3 18F-FDG
18F-FDG 18F-FDG-2-P k2 k4 k4 unfixed C2 C1 Cp k4 fixed(k4=0)
dephosphorylation blood activity tissue activity uCi/mL uCi/mL
Dynamic FDG imaging Time (min) Radioactivity decay corrected Time
(min) compartment modeling Blood activity data (.tot files and .cor
files)
INPUT Blood activity data (.tot files and .cor files) Tissue data
(.mic files) ROI list OUTPUT K1, k2, k3, k4 Compartment modeling
was performed after fixing and unfixing the k4 values Number of
subjects FAD subjects Control FAD subject SWM region K4 fixed K1=
K2= K3= K4=0 K1/k2= DV= 0 k3 values k1/k2 in FAD subjects (k4
fixed)
FDG (plasma) FDG (tissue) FDG-P (tissue) k2 k3 values k1/k2in FAD
subjects (k4 fixed) Degree of phosphorylation of FDG degree of
perfusion/tissue extraction Regions k1/k2 and k3in control
subjects
k3 values k1/k2 values degree of phosphorylation degree of
perfusion/ tissue tracer extraction Control Vs FAD subjects
K3 values in the SWM region in subjects and control (k4 fixed)
Subjects K3 value Average STDEV C1 C2 0.0349 h3537 h3671 h3691
h3762 h3810 15.5% Phosphorylation of FDG contributes to the
observed decreased in the FDG uptake in FAD subjects compaed to
control subjects (SWM region) K1/k2 in the FAD subjects are higher
than in the controls
Average STDEV C1 0.3583 0.3684 C2 0.3785 h3537 0.5286 0.5194 h3671
0.4807 h3691 0.5356 h3762 0.3942 h3810 0.6579 The perfusion or
tissue tracer extraction does not contribute for the observed
decrease in the FDG uptake in FAD subjects (SWM region) Fraction of
phosphorylation = k3/(k2+k3)
(fraction of FDG undergoing phosphorylation) k1 k3 FDG (plasma) FDG
(tissue) FDG-P (tissue) k2 k4 K4 fixed Subjects k3/(k2+k3) Average
STDEV C1 C2 h3810 h3762 h3691 h3671 0.3048 h3537 8.5% Application
to my research-experimental therapeutics
Tissue targeted encapsulated agents eg. Tumor targeted
nanoparticles carrying drugs v vvv tumor tissue v vvv Drug
resistance v vvv nanoparticles (plasma) perfusion nanoparticles
internalized in tumor cells Conclusions 2 tissue compartment model
was applied to the 18F-FDGadministered FAD and normal subjects. Our
analysis represented a lower k3 values in the SWM region inFAD and
in control subjects compared to other cortex regions. The values of
k3(degree of phosphorylation) in the FAD subjectsin the SWM region
is lower than in control by 15% The fraction of FDG undergoing
phosphorylation in FADsubjects we analyzed was 8.5 % lower than in
control subjects. Thanks Dr. Seong-Gi Kim Dr. William Edy
Dr.Charles Laymon (mentor)
Department of Radiology Carl Rhaven Dr. William Klunk Department of
Psychiatry