Improving PET Image Quality and Quantification by Using Motion Correction, Parametric Imaging and MAP Reconstruction
Phase: PHASE4
Conditions: Brain Imaging, Whole Body Imaging
Sponsor: Mayo Clinic

 
 
Improving PET Image Quality and 
Quantification by Using Motion Correction, 
Parametric Imaging and MAP Reconstruction 
 
NCT04417998 
 
May 3, 2024 

Title: Improving PET Image Quality and Quantification by Using Motion Correction, Parametric 
Imaging and MAP Reconstruction 
 
Principal Investigator: Bradley J. Kemp, PhD 
 
Co-investigators:  
, MD 
 
 
 
, MD 
 
 
 
, MD 
 
 
 
, MD 
 
Study Coordinators: 
 
 
 
 
 
 
 
 
Jessica L. Brunn 
 
 
 
 
 
 
 
Amy Bastian 
 
Protocol: 
 
Prior Version 1.0; November 29, 2019 
Prior Version 2.0; November 10, 2020 
 
 
 
Prior Version 3.0; January 4, 2023 
 
 
 
Prior Version 4.0; April 26, 2024 
Current Version 5.0; May 3, 2024 
 
 
1. Background 
Positron emission tomography (PET) plays an important role in brain imaging as PET images provide quantitative 
measurements of uptake of a radiopharmaceutical. Important in vivo physiological measurements pertinent to 
cognitive impairment, such as metabolic rate of glucose and deposition of amyloid plaques and neurofibrillary tangles, 
can be measured using 18F-FDG, 11C-PiB and 18F-AV1451 PET imaging, respectively. 
The accuracy of these quantitative measurements depends on factors such as spatial resolution and attenuation 
correction, and it also depends on patient compliance.  Patient motion during a PET brain study will degrade image 
quality and reduce the accuracy of quantitative measurements of radiopharmaceutical uptake in regions of the brain. 
It is hypothesized that motion correction will improve the quantitative accuracy of PET brain studies. 
The accuracy of quantitative measurements also depends on the type of data acquisition and the method used 
to analyze the data.  Static PET images can be used to quantify uptake at a single point in time whereas dynamic 
images and compartmental modeling can be used to create parametric images that represent kinetic parameters 
such as blood flow, blood volume, receptor density or metabolic rates.  Parametric imaging has remained a research 
tool as the scans are lengthy in duration and the analysis is involved. Static imaging is more practical in terms of 
patient throughput and image interpretation but it can overestimate uptake of a radiopharmaceutical.  Therefore, there 
is renewed interest in applying dynamic imaging and compartmental modeling in clinical studies. It is hypothesized 
that dynamic imaging in clinical studies will assist in the diagnosis of tumors with low uptake or tumors in high 
background regions. 
PET image quality and quantitative measurements are also influenced by the reconstruction algorithm used to 
create the images. Statistical iterative reconstruction (IR) algorithms that incorporate corrections for attenuation, 
scatter and spatial resolution have been shown to improve image quality and quantitative measurements over analytic 
algorithms such as filtered backprojection. Incorporating time-of-flight information into an IR algorithm further 
improves the signal to noise ratio of the reconstructed images. Statistical IR reconstruction algorithms need to run 
through a large number of iterations in order to achieve convergence and provide accurate quantitative information. 
Unfortunately, the noise in increases as the number of iterations increases which creates images of poor diagnostic 
quality.  Maximum a posterior (MAP) or regularized reconstruction algorithms have been developed to suppress 
noise. These algorithms use penalty functions to model a prior information about the reconstructed image and a 
weighting parameter that controls the influence of the prior constraint and thus the amount of image smoothing, edge 
preservation and low contrast detail. It has been shown that regularized reconstruction algorithms increase lesion 
conspicuity and improve the accuracy of quantitative PET measurements. 

 
Motion Correction 
Patient motion during a PET brain study will degrade image quality and reduce the accuracy of quantitative 
measurements of radiopharmaceutical uptake in regions of the brain.  In addition, patient motion has a more 
pronounced effect on uptake measurements as the spatial resolution of PET systems improves and regions of interest 
become smaller; both issues are important in PET brain imaging. PET brain imaging of subjects with dementia is 
vulnerable to motion as the scans are long in duration and the subjects are prone involuntary motion. Head restraints 
are used reduce the amount of motion but do not eliminate it. For example, slow changes in head position and 
orientation can occur as patients gradually relax as the scan progresses. 
Typically, a PET brain study is acquired as a dynamic scan that is comprised of individual frames. A technologist 
will subjectively assess for patient motion by visual comparison of the position and orientation of the head in each 
frame. If it is deemed that the patient remained still then all frames will be summed together to create a static image. 
However, if it is deemed that a patient moved then the frames that contain motion will be discarded and not used to 
create the summed static image. 
Ideally the motion correction process should be fully-automated and objective and any frames that contain motion 
would be realigned and summed with the non-motion frames instead of being discarded. Moreover, proper motion 
correction should also realign the PET images to the CT images in addition to realigning the individual frames of the 
dynamic PET images. This will ensure accurate quantification of uptake measurements as the CT images are used 
to correct the PET data for attenuation.   
Motion can be estimated by constantly monitoring the head position and orientation during the PET scan through 
the use of external-tracking devices or data-driven methods.  The latter approach uses the raw PET data itself to 
measure the motion. Data-driven methods are attractive as no external equipment is necessary (less setup time, not 
cumbersome to use) and motion compensation can be applied retrospectively.  The effectiveness of data driven 
motion correction will depend on the temporal sampling of the raw data, the statistical quality of the raw data and 
whether the radiopharmaceutical distribution changes during a study. In this research study the Siemens data-driven 
motion correction algorithm will be evaluated in patients undergoing PET brain scans using radiopharmaceuticals 
18F-FDG, 11C-PiB or 18F-AV1451.  
 
Parametric Imaging 
In PET imaging various quantitative physiological in vivo measurements can be made depending on the purpose 
of the study, the radiopharmaceutical and acquisition technique employed. A quantitative measurement can be made 
from a single time frame or static image in which the patient is scanned at a specific time after radiopharmaceutical 
administration; one such measure is the standard uptake value, SUV, which represents the amount of uptake of 
radiopharmaceutical normalized to the amount of radiopharmaceutical administered and the weight of the patient.  
Alternatively, quantitative measurements can be made from a dynamic scan in which the uptake of a 
radiopharmaceutical is measured over time and kinetic parameters such as blood flow, blood volume, receptor 
density and metabolic rates are subsequently derived from compartmental modeling. (Note that the dynamic scan 
used in the context of motion correction is a coarse temporal sample scan used to assess patient position and not 
model radiopharmaceutical kinetics).  Compartmental modeling requires dynamic PET scans of long duration: the 
scan starts at administration of the radiopharmaceutical and continues through the wash-in and wash-out phases of 
the radiopharmaceutical. Compartmental modeling generally requires an input function that represents the 
concentration of radiopharmaceutical in the arterial blood supplying the organ of interest. Input functions can be 
obtained invasively from arterial blood samples or alternatively an image-derived input function is obtained either 
from the left ventricle, aorta or carotid artery.  When the compartmental model is applied, voxel-by-voxel, to every 
voxel in a 3-D PET volume, parametric images of the resulting kinetic parameters are obtained.  For example, the 
metabolic rate of glucose can be measured with 18F-FDG and the parametric image shows the 18F-FDG metabolic 
rate in each voxel, rather than uptake.  
Computation of kinetic parameters for models that use two tissue compartments (metabolized and unmetabolized 
radiopharmaceutical) is time consuming as non-linear data fitting procedures are required to solve coupled differential 
equations. The analysis can be accelerated by linearization, whereby linear least squares fitting procedures are used 
for the parameter estimation. Patlak and Logan analyses are two ‘linearized’ methods for estimating kinetic 
parameters for radiopharmaceuticals that are irreversibly and reversibly bound in the metabolized compartment, 
respectively. Patlak analysis is used for measurement of metabolic glucose rate using dynamic 18F-FDG scans 
whereas Logan analysis is used to quantify the distribution volume and binding potential of 18F -AV1451.  Static 
imaging is preferred over dynamic imaging for clinical imaging because the acquisition is quick and SUV analysis is 
simple. However, static imaging and SUV analysis is a surrogate for glucose metabolism as it measures the total 
radiopharmaceutical uptake and does not differentiate between metabolized and non-metabolized 18F-FDG in the 

blood and intracellular spaces (ie specific or non-specific uptake) or the plasma dynamics. Patlak analysis of 18F-
FDG measures the metabolized 18F-FDG and, unlike SUV analysis, is independent of the scan time after 
administration of 18F-FDG. 
There is renewed interest in parametric imaging in clinical oncologic studies involving tumors with low uptake or 
tumors in high background regions. Siemens have implemented an automated workflow for parametric imaging on 
the Biograph Vision 600 PET/CT system called FlowMotion Multiparametric PET Suite. Patlak analysis is the only 
analysis method currently available in the parametric imaging package. The fully-automated acquisition protocol 
proceeds as follows. First the system will obtain an input function by acquiring dynamic images of the left ventricle as 
the radiopharmaceutical is administered. Next eighteen dynamic images are acquired by automatically shuttling the 
imaging table and scanning the patient multiple times.  For clinical oncologic studies this second phase is a series of 
whole body acquisitions while for a brain studies the second phase is a series of brain acquisitions, and for all studies 
the second phase includes imaging the left ventricle for the input function. The entire process requires minimal 
operator intervention once the scan ranges are prescribed. The output of the workflow are parametric images 
generated from Patlak analysis.  Alternatively, for radiopharmaceuticals that require Logan analysis, the raw dynamic 
images can be exported to off-line compartmental modeling software. In this research project the data acquisition 
and image processing workflow for quantitative parametric analysis of brain and whole body scans will be assessed. 
Further, the development of in-line Logan parametric analysis will be conducted using patient data. 
 
2. Methods 
2.1. Subject Enrollment 
Inclusion Criteria 
1. 18 years of age or older 
2. Subjects who are able and willing to sign the informed consent 
3. Subjects who are able to follow verbal commands 
4. A negative urine pregnancy test within 48 hours prior to PET imaging procedures in females of 
childbearing potential 
5. Subjects who are scheduled for a PET/CT study under Mayo Clinic Rochester IRB research protocol 
08-005553 (Aim 1 cohort only) 
6. A positive 18F-FDG oncology PET/CT exam in the last two months (Aim 2 cohort only) 
 
Exclusion Criteria 
1. Patients who are unable to lay still for an additional 15 minutes (for Aim 1 cohort) 
2. Patients who are unable to lay still for up to 90 min for 18F-FDG scans or up to 100 min for 18F-AV1451 
scans (for Aim 2 cohort) 
3. Patients who cannot follow the prep instructions 
 
2.2. Aim 1: Motion Correction Cohort 
2.2.1.  Subject Enrollment 
Aim 1 involves the prospective data collection of subjects who are already enrolled in Mayo Clinic 
Rochester research study 
(PI: Dr 
) and are scheduled to be scanned on the Siemens 
Biograph Vision 600 PET/CT system (hereafter referred to as the V600-R1) in the PET/CT Molecular Imaging 
Research Center on Charlton 6 of Mayo Clinic Rochester. To be clear, this is a separate research study in 
which the
subjects will be enrolled. In the interest of time subjects will be recruited for this research 
study and will provide written consent prior to their 
 study. 
2.2.2. Number of Subjects 
We plan to successfully scan 30 subjects for Aim 1. Subjects enrolled in research study 
 
are administered one of the radiopharmaceuticals 18F-FDG, 11C-PiB or 18F-AV1451 per exam. For this 
research study we will successfully scan 10 subjects with one of the radiopharmaceuticals for a total of 30 
scans in 30 subjects. The purpose of this pilot research protocol is to evaluate the effectiveness of motion 
correction and therefore the sample size is not designed to measure a statistically significant difference 
between subjects scanned with and without motion. 
It is important to note that the subjects will not receive a second 18F-FDG, 11C-PiB or 18F-AV1451 
radiopharmaceutical injection for this research study – the residual radioactivity from their 
 study 
is adequate.   

2.2.3.  Subject Scanning 
Upon completion of their 
study the subjects will be asked if they would like to continue with 
this research study. If the subjects agree they will remain in Charlton 6. They will be given the option of 
remaining on the scanning table or having a short break. The data collection for this research study will 
commence immediately thereafter. 
A new exam will be created on the V600-R1 under which the enrolled subjects will be scanned; as 
mentioned this new exam is a stand-alone, separate exam from the 
 study. The subject will be 
positioned on the imaging table with their head in a head-holder and with their arms by their sides. The helical 
CT-portion of the PET/CT scan, used for PET attenuation correction (ie a ‘CTAC’ scan), will then be acquired.   
Next a 10 min PET scan will be acquired. During the first 3 to 5 min of the PET scan the subjects will remain 
motionless; this will serve as a baseline reference scan. For the remainder of the scan the subjects will be 
instructed to move. The motions will include slow oscillating rotations, rapid rotations and translations of 
various magnitudes. The PET system acquires data in list mode; this allows the data to be retrospectively 
binned into scans with variable start times and durations. 
All PET and CT data acquired under this research study will be transferred to a private PET research 
partition within PACS. In addition, all PET and CT data will be de-identified and renamed on the PET/CT 
scanner console. This process creates a copy of the study with all identifiers removed and replaces the 
subject name and ID with a numerical code. PET and CT data from the de-identified study will be sent to a 
separate workstation for off-line image reconstruction using Siemens E7 Reconstruction Tool and analysis.  
2.2.4.  Image analysis 
The motion-corrected reconstructed images acquired when the subject was moving will be 
quantitatively compared to the baseline reference reconstructed images acquired when the subject was 
instructed to remain still. Metrics such as radiopharmaceutical uptake, contrast to noise ratio and effective 
spatial resolution will measured. Qualitative assessment of image quality and presence of artifacts will be 
performed by Dr 
.  
 
2.3. Aim 2: Parametric Imaging Cohort 
2.3.1.  Subject Enrollment 
Aim 2 involves the prospective data collection of subjects undergoing brain or whole body oncologic 
PET/CT scans on the V600-R1.   
2.3.2.  Number of Subjects 
We plan to successfully scan up to 30 subjects for a total of up to 35 PET/CT scans. Specifically, we 
plan to collect up to ten 18F-FDG brain scans, up to ten 18F-FDG whole body oncologic scans and up to ten 
18F-AV1451 brain scans. The research studies will be performed less than two months from a positive clinical 
finding. Up to five of the subjects in the 18F-FDG whole body oncologic cohort will undergo a repeat study 
within a week of their initial research study.  
The purpose of this pilot research protocol is to evaluate the data acquisition and image processing 
workflow and therefore the sample size is not designed to measure a statistically significant difference 
between subjects. 
2.3.3.  Subject Preparation 
Patients will be given prep guidelines to follow prior to reporting to Desk 6B in the PET/CT Molecular 
Imaging Research Center on Charlton 6 of Mayo Clinic Rochester. The subject will be positioned on the 
imaging table with their head in a head-holder and with their arms by their sides. A CTAC scan, used for PET 
attenuation correction, will be acquired.  Immediately following the start of the PET scan, a 
radiopharmaceutical dose will be administered intravenously using an infusion pump followed by a saline 
flush. The administered radiopharmaceutical radioactivity will be 8 ± 10% mCi 18F-FDG or 9 to 11 mCi 18F-
AV1451 for brain scans or 10 ± 10% mCi 18F-FDG for oncology scans. The first 6 min of the PET scan 
consists of a dynamic acquisition over the heart for measurement of the input function. This is followed by up 
to 20 brain plus heart passes for patients receiving a parametric brain scan or up to 20 passes from orbits to 
thighs (which includes the heart) for patients receiving a parametric whole body scan. The total PET scan 
duration will be up to 90 min for 18F-FDG scans and up to 100 min for 18F-AV1451 scans. 
As described in Aim 1, all PET and CT data acquired under this research study will be transferred to 
a private PET research partition within PACS. In addition, all PET and CT data will be de-identified and 
renamed on the PET/CT scanner console. This process creates a copy of the study with all identifiers 
removed and replaces the subject name and ID with a numerical code. PET and CT data from the de-
identified study will be sent to a separate workstation for off-line analysis.  

2.3.4.  Feedback Questionnaire 
After completion of a patient study the PET technologist will complete a questionnaire that assesses 
the data acquisition workflow. Topics such as ease of prescribing the PET/CT exam, starting and monitoring 
the scanning, reviewing images and overall process of acquiring the scans will be rated on a scale of 1 to 5, 
with 1 being challenging and 5 being easy. 
2.3.5.  Image analysis 
The metabolic rate of 18F-FDG shown in the parametric images will be compared to SUV from static 
images (ie a single scan from one of the up to 20 passes). Also, the parametric images created with the 
measured input function will be compared to parametric images created with a generic, population-based 
input function. The dynamic series will be analyzed using dedicated compartmental modeling software 
(PMOD ver 3.5; PMOD Technologies, Zurich); the metabolic rate of 18F-FDG from the parametric images will 
be compared to the metabolic rate computed using Patlak and two compartment models in PMOD.  Logan 
analysis in PMOD will be used to compute the distribution volume and binding potential of the 18F-AV1451 
dynamic scans.  In addition, the motion correction software developed in Aim 1 will be used for the parametric 
brain images. 
 
2.4. Aim 3: MAP Reconstruction Cohort 
This aim does not require the prospective collection of patient studies. A total of up to 30 whole body 
and brain PET studies will be evaluated retrospectively. PET raw data acquired as part of any research study 
on the V600-R1 system can be used; this includes studies acquired for Aim 2 and for other whole body 
research studies acquired on the V600-R1. In order to increase the number of studies, de-identified clinical 
patient studies acquired on the Siemens Biograph Vision 600 PET/CT system installed in Nuclear Medicine 
on Charlton 1 (to be installed January 2020) can also be used. 
As described in Aim 1, PET and CT data will be de-identified and renamed on the PET/CT scanner 
console. This process creates a copy of the study with all identifiers removed and replaces the subject name 
and ID with a numerical code. PET and CT data from the de-identified study will be sent to a separate 
workstation for off-line MAP reconstruction using Siemens E7 Reconstruction Tool and analysis. 
2.4.1.  Image Review 
An appropriate image review such as a single-reader, visual, blinded image quality assessment (or 
other methods to be identified upon consultation with Siemens) will be performed. Results of MAP 
reconstruction analysis will not be reported or entered into the patient’s clinical record. 
 
3. Data Archival 
All subject data will be archived on an external password protected and encrypted hard drive.  All 
reconstructed image data will be transferred to a DICOM archive system for long-term storage.  De-identified 
data will also be transferred to Siemens Healthineers via encrypted data transmission. As required by HIPAA and 
described above, the study will be de-identified prior to secure transmission to Siemens. 
 
4. Risks and Benefits 
4.1. Reasonable Foreseeable Risks or Discomforts to the Patients 
4.1.1. IV:  The risks of IV placement in Aim 2 may include:  discomfort at the site of puncture, possible 
bruising and swelling around the puncture site, infection (rarely), and (uncommonly) faintness from 
the procedure. 
4.1.2. Fear of Confined Spaces:  Some participants may experience anxiety in the PET/CT scanner; 
participants will be monitored throughout the scan by the imaging technologist, and scans will be 
stopped immediately for any participant who is unable or unwilling to continue the procedure. 
4.1.3. Radiation Risks:  The PET/CT procedure of Aim one involves 1 CTAC scan (low-dose CT scans for 
PET attenuation correction) of the head. A single PET/CT procedure in Aim 2 involves one CTAC 
scan of the head plus one CT scan of the chest or one whole body CT scan, and it also involves one 
administration of either 18F-FDG or 18F-AV1451.  
4.1.4. Risk of Disclosure of Protected Health Information:  Safeguards against the risk of disclosing protected 
health information (PHI) include ensuring all data that contain PHI remain within Mayo Clinic.  The 
imaging data will be stripped of all identifying information and assigned a numerical code before the 
images are transferred from the enterprise.  Only de-identified information will be shared with the 
Siemens Healthineers.  Patient consent forms will be stored in locked files in the office of the study 

coordinator and/or principal investigator, and no identifying information will be available to personnel 
outside of the coordinator(s) and institutional investigators. 
4.1.5. Potential Benefits to Society and Participants (not including compensation): Participants in the study 
will not receive any direct medical benefit. 
4.1.6. Costs to Participants from Participating in Research: Subjects will not incur any costs by participating 
in this research study.  
4.2. Compensation to the Participants: Subjects enrolled in Aims 1 will be remunerated $
 for their participation 
in the study. Subjects enrolled in Aim 2 will be remunerated $
; those subjects who undergo a repeat 
study will receive an additional $
. 
 
5. Data Safety Monitoring Board (DSMB) 
A DSBM is not required for this protocol.  The risk to the subjects in Aim 1 is from the dose of the non-
 
diagnostic CTAC scan, which can be considered low.  The risk to the subjects in Aim 2 is from the dose of 
the radiopharmaceutical and non-diagnostic CTAC scan. Further, this protocol does not involve a large number 
of subjects, multiple study sites, or highly toxic therapies or dangerous procedures.