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					                                       RSNA R&E Foundation Education Scholar Grant
                                                 SAMPLE APPLICATION

NOTE: Personal information for the applicant and other investigators has been removed from this sample application.

Title:

CT Virtual Autopsy for Radiation Dose Reduction and Radiological-Pathological Correlation Training Programs

Abstract:

Postmortem examinations generally show an error rate for clinically significant conditions in approximately 20-30% of
postmortem examinations in most studies. Despite this there has been a continuing decline in the rate of autopsies,
with academic institutions having an autopsy rate of 10-20% and community hospitals having an autopsy rate in
many cases bordering on zero. This error rate has occurred despite modern laboratory and radiology testing including
cross-sectional imaging techniques. Because postmortem radiographic examination may be more acceptable to next
of kin of deceased and possibly also to attending physicians, one step in reversing the decline of information that
could be obtained only by autopsy is correlation with assistance from imaging techniques after death. Recently, use
of CT and MRI has been described for postmortem imaging (virtopsy) in conjunction with autopsy. Virtopsy can add
information to the autopsy and enable a more focused autopsy. Yet in most academic institutions, benefits of
virtopsy have not been exploited. Our proposal seeks to address this discrepancy, by developing two model training
programs for radiologists, residents and medical students. The first program will use imaging data acquired from CT
virtopsy at different radiation dose levels through different body regions to develop a training module for educating
radiology personnel on perception of pathologically proven abnormalities at different levels of radiation doses. Unlike
antemortem CT, postmortem CT can be repeated several times without risks to the body and would not require
simulated low dose images which are not ideal with greater level of radiation dose reductions in our experience. The
second program will create a teaching module of two and three dimensional CT and MR imaging data with relevant
photographic documentation from gross and microscopic autopsy examinations. The latter module will help enhance
understanding of the radiologic and pathologic correlation of different disease processes leading to death.

Percent of Time Dedicated to this Project:

(Not included in sample)

PriorityStatement:

Priority Statement: Over the past 8 years I have dedicated my research efforts to learning, researching and educating
different aspects of CT radiation dose. Following my residency in Diagnostic Radiology in one of the premier healthcare
institution in India, I joined Massachusetts General Hospital in 2001 to work on newer agents for MR imaging of liver. As
things unfolded upon my arrival in Boston, I was asked to work on CT radiation dose optimization and technology
assessment projects. From that point onwards, I have dedicated my research efforts to CT radiation dose reduction and
technology assessment research. During my research with radiation dose I performed a number of phantom and patient
studies as well as post mortem CT studies for dose reduction purposes. After writing more than 75 original research
articles, reviews, editorials and book chapters and editing four textbooks and peer reviewing several journals, I single
handedly started a two day CT radiation dose education course for CT technologists and radiologists giving 14 lectures in
a day and half course in September 2009 and again in November 2009. These courses made me realize that I have
always loved teaching. I have started work on developing radiation dose training software at our institution to emphasize
and highlight how training can help improve the attitude and comfort of radiologists to low radiation dose CT images. In
order to enhance the educational aspect of scientific peer review journal, as a special consulting editor to the American
Journal of Roentgenology’s Resident Review section, I proposed an innovative format for structured reviews for education
of radiology residents and fellows. Going forward from this point of my career, I intend to make new techniques and fields
of radiology education as my priority. As an instructor in Radiology for the Harvard Medical School and an Assistant
Radiologist in Massachusetts General Hospital, I am involved with teaching and training of the residents and fellows-
tasks that I really enjoy and look forward to. In addition, from January to April 2010, I will serve as a visiting fellow at the
Center for Medical Image Sciences and Visualization (CMIV) at Linkoping University, Linkoping, Sweden and work on a
number of radiation dose reduction, CT and MR image processing techniques, as well as postmortem imaging (virtopsy)
projects. In this period, I will work under the guidance of Dr. Anders Persson, Director of the CMIV and one of the
pioneers in field of virtopsy and image processing. I believe that during my stay in Linkoping University, I will gets hands
on experience in the fine details of virtopsy with CT and MR imaging as well as existing and upcoming techniques for
these examinations. With the proposed project, I wish to accomplish to two important tasks. Firstly, address the issue of
educating upcoming and established radiologists on effect of low and standard radiation dose on image quality and lesion
characteristics. This training program will provide them with the confidence of interpreting low dose CT examinations,
which I believe is a crucial precursor to all low dose endeavors. CT radiation dose reduction has been a priority for
Massachusetts General Hospital since several years. Secondly, with the virtopsy, I wish to open a new opportunity for
training upcoming radiologists and expand the horizons of imaging beyond the living but in directions that will ultimately
help patients as well. Having personally attended several conventional autopsies and autopsy conferences, I have
realized that the experience of witnessing the “truth being exposed” on the autopsy table or under the microscope has
tremendously enhanced my understanding of radiology. This insight into the pathology division gives me the confidence
that ultimately a teaching curriculum aimed at radiological-autopsy-pathology correlation will add tremendously to the
quality of current radiology education curriculum. In addition, as published literature has revealed radiology modalities can
add information to that obtained from autopsy in a non-invasive manner. Both the departments of MGH Imaging and
Pathology have indicated their support, willingness and eagerness to support and enhance the virtopsy project and
educational endeavors. My long term goal is to develop these educational programs and models as an example and a
resource for other institutions in the country and world. I also envision that these projects will help me enhance advance
my career as an educator and a visionary for developing practical and novel educational activities in radiology which have
true and immediate benefits for our patients.

Budget:

(Budget details have been removed from this sample)

PI Salary Support
Research Assistant
LCD Display 4MP
Mac Pro Quad-Core Xenon CPU
Artifact-Free Body Bags for CT
320 GB External Hard Drives (4)

Other Investigators:

Name: Abhinav Vij, MBBS, MPH
Position: Research Fellow, Radiology, Massachusetts General Hospital, Boston, MA
Role in the Project: Dr. Vij will be responsible for the coordination between the Departments of Pathology and
Radiology for actual performance of virtopsy. He will assist in transportation and CT scanning of the
subject’s body. Dr. Vij will play an important role in image transfer, image interpretation, maintenance of
case record files, CT and conventional autopsy data compilation, data analysis, preparation and submission
of the manuscripts. He will be involved in the educational component of the project, where his qualifications
as a Masters in Public Health will play an important role. He will be responsible for development of online
educational program for educating other radiologists, residents and fellows on interpretation of findings on low
dose CT scanning.

Name: Eugene J. Mark, MD
Position: Director of the Autopsy Service and Deputy Medical Examiner, Department of Pathology, Massachusetts
General Hospital, Boston, MA
Role in the Project: Dr. Eugene Mark will serve as a scientific advisor for this project. He will be responsible for
conducting the conventional autopsies on the study participants. As director of autopsy services at the MGH with several
years of valuable experience and impeccable standing, Dr. Mark has obtained full support and consent of the Pathologist-
in-Chief at the MGH for the proposed project. In addition, Dr. Mark will help in logistics of virtopsy of the subjects, and will
actively participate in educational component of the project and contribute actively in correlative research
projects as outlined in the detailed plan. His support and contribution is a key to the success of the proposed
project.

Name: Anders Persson, MD, PHD
Position: Director, Center for Medical Image Science and Visualization (CMIV), Linköpings University, Sweden
Role in the Project: Dr. Persson will serve as a Scientific Advisor for the proposed project.
Dr. Persson and his collaborator at University of Bern, Dr. Michael Thali are perhaps two of the foremost
experts in the world on virtopsy. With multiple research and educational publications and hands on
experience in virtopsy over the past several years, Dr. Persson will mentor Dr. Mannudeep Kalra from
January to April 2010 on logistics, scanning techniques, image interpretation and educational aspects of
virtopsy for the duration of Dr. Kalra’s stay at the Linkoping University. For the duration of the proposed
project, Dr. Persson will actively advise on both educational and research aspects of the project.
Name: James H. Thrall, MD
Position: Radiologist-in-Chief, MGH Imaging, Massachusetts General Hospital, Boston, MA
Role in the Project: Dr. James Thrall, Chairman and Professor, MGH Imaging and Harvard Medical School, will serve
as an educational scientific advisor for the project. Dr. James Thrall is regarded as one of the most
prominent radiologist and educator in the world. Support and guidance of Dr. Thrall has helped us obtain the
necessary permissions for imaging subjects scheduled for conventional autopsies and has extended his
support for developing educational and research components of the project.

Detailed Education Plan: (See Next Page)
CT virtual autopsy for radiation dose reduction and radiological-pathological correlation
training programs

A. Detailed Education Plan:
• Rationale and Purpose: General statement of purpose-
1. To develop an educational program on CT radiation dose using CT data acquired at multiple dose
    levels in deceased subjects who undergo conventional autopsy examination and receive pathologic
    confirmation of lesions or abnormalities.
2. Integration of pre-mortem and post mortem imaging studies and pathology services for correlating
    radiologic images and autopsy findings for educational purposes.

• Reasons the project should be undertaken:
To develop an educational program on CT radiation dose using CT data acquired at multiple dose
levels in deceased subjects who undergo conventional autopsy examination and receive pathologic
confirmation of lesions or abnormalities. CT radiation dose reduction is one of the most important
issues concerning the radiology departments around the world primarily due to risk of radiation induced
carcinogenesis. Data suggest that number of CT examinations performed each year have grown by
almost 750% in the last two decades [1]. Indeed, the annual radiation exposure has nearly doubled to
6.2 mSv from 3.6 mSv in 1980 primarily due to increased utilization of CT imaging in modern medical
practice [2]. It is estimated that in 2006, about 62 million CT examinations were performed in the United
States alone [1]. Given the fact that radiation induced carcinogenesis is stochastic effect; the probability
its occurrence is directly related to the amount of radiation dose [3-7]. In other words, a decrease in
radiation dose with CT will decrease the probability of occurrence of radiation induced cancer. While
benefits of CT scanning in terms of diagnostic information can not be denied, one can also not deny the
fact that much of the diagnostic information from CT scanning can be obtained at much lower dose than
being used presently. There is also 4 to 8 folds variability in the amount of radiation dose associated
with CT exams of the same body regions performed in different institutions [8]. Several investigations
have shown that this variability increases radiation dose to patients [8, 9]. This wide variability of
radiation dose may be due to lack of understanding of complex scanning parameters and their effects
on image quality and artifacts. A decrease in radiation dose is associated with an increase in the image
noise and with excessive dose reductions artifacts are also possible. However, several studies have
shown that with help of manual adjustment of scanning parameters, radiation dose can be reduced
while retaining the diagnostic information [10-14]. Vendors have also initiated and developed
technologies to reduce radiation dose. Our group has also performed several studies on CT dose
reduction with both manual adjustment of scanning parameters as well as using the technologic
developments such as iterative reconstruction, noise reduction filters, automatic exposure control
techniques, and automatic centering or vertical positioning software [15-34]. There has been however a
noticeable lack of a well defined educational component to enhance understanding of low radiation
dose CT amongst the practicing and in-training radiologists, as was also recently highlighted in the
White paper on CT radiation dose published by the American College of Radiology [35]. Recently, we
have attempted to dose training software programs to educate and enhance confidence of radiologists
for interpretation of low radiation dose CT images [36, 37]. Such software have relied on use of noise
projection software, which add noise to images acquired at much higher dose levels to obtain simulated
low dose CT images. In our experience, such noise projection software works well only for simulating
images with less than 50% dose reductions. They do not work well with greater levels of dose
reductions and also do not produce artifacts that may be seen on “true” lower dose images.
Simultaneous acquisition of images at multiple dose levels in live subjects is not feasible as such
examination will increase radiation dose to the participating subjects. For CT virtopsy however, there
are no concerns for radiation induced adverse effects and repetitive scanning at multiple dose levels
can be easily performed. Also subjects undergoing postmortem CT scanning will have pathology
confirmation of lesions seen on CT images. These are reasons we believe that multiple “true” low and
standard postmortem CT examinations can provide good datasets for low dose CT training programs.

Integration of ante-mortem and post mortem imaging studies and pathology services for correlating
radiologic images and autopsy findings for educational purposes: Despite advances in both
                                                         1
antemortem pathology and radiology techniques, several studies point out to the fact that in both adults
and children a substantial number of antemortem diagnoses are incorrect [38-45]. These studies use
conventional autopsy as their standard of reference and point out to the relevance of the conventional
autopsies even in the current state of medicine. Despite these reports, it is widely believed that the rate
of conventional autopsies around the world has been decreasing [38, 45]. For past several decades,
premier academic and teaching hospitals including the Massachusetts General Hospital and institutions
such as Armed Forces Institute of Pathology’s Department of Radiologic Pathology hold radiology
pathology conferences to underscore the importance of correlating imaging findings with pathology.
Recently, several investigators have emphasized role of CT and MR imaging in evaluation of non-
homicidal, homicidal, accidental, as well as suicidal deaths as a complementary technique to autopsy
[46-70]. In light of these studies, our department chief has allowed us to perform CT and/or MR Imaging
in cadavers who are scheduled for conventional autopsy. While CT offers information regarding the
airways, lungs, bones and metallic implanted and foreign bodies, MR due to its superior contrast
resolution enables better delineation of soft tissue abnormalities without need of intravenous contrast
materials [51, 53, 55, 67, 69]. To our best knowledge, most radiology departments do not offer
opportunity for correlation of imaging findings with autopsy findings except on a limited scale during the
radiologic pathology conferences. Since attending the weekly autopsy conferences in the Mass General
Hospital’s Department of Pathology, like several other investigators, we too have realized that there is a
tremendous advantage for correlating antemortem and postmortem imaging findings with results of
conventional autopsy. Such correlation will help identify the “what” in radiology reports with “why” and
“how” from the conventional autopsy table. Published studies have also shown that virtopsy with CT
and/or MR imaging provide tremendous help in determining cause and effects of terminal event in life
[46-70]. In fact, additional and complementary information can be obtained with imaging following
death. Levy et al have reported use of CT virtopsy to evaluate mode and cause of death following war
related death of the US army personnel in Iraq and Afghanistan [49]. Likewise, postmortem CT and MR
imaging has also been found to add valuable information in several cases of strangulation, drowning,
vehicular accidents, bullet injuries, stab wounds, child and elderly abuse, and burns. These studies
highlight the growing relevance of postmortem imaging [49-70].

• Objectives:
   1. To develop an educational program on CT radiation dose using CT data acquired at multiple
       dose levels in deceased subjects who undergo conventional autopsy examination and receive
       pathologic confirmation of lesions or abnormalities.
   2. Integration of pre-mortem and post mortem imaging studies and pathology services for
       correlating radiologic images and autopsy findings for educational purposes.

• Student Population:
Practicing and in training (residents and fellows) radiologists will be the learner groups served by the
project. This project will help them understand the effect of radiation dose on image quality and most
importantly on detection of autopsy proven lesions in different part of the body. Although it is true that
post mortem CT will lack the dynamic contrast enhanced image dataset, our postmortem low dose CT
studies will overcome the limitation of most prior studies which lack pathology or autopsy correlation
while generating true (non-simulated) images at multiple levels of reduced radiation dose. Such unique
training will help us explain the effect of scanning parameters on radiation dose, image quality,
diagnostic confidence and artifacts. Development of an educational curriculum for imaging (CT and
MRI) and autopsy correlation will help the practicing and in training radiologists to understand the
postmortem imaging findings as well as understand the concepts of antemortem and postmortem
imaging correlation with autopsy.

• Previous Experience:
Dr. Mannudeep K. Kalra, Director of the Center for CT Dose Optimization, Support and Education at
the MGH (CTDOSE@MGH), has tremendous experience in CT radiation dose education and research.
Dr. Kalra has assessed and published several CT dose reduction strategies and techniques including
weight based dose reduction with fixed tube current as well as automatic exposure control techniques,
He has also investigated indication based adjustment of automatic exposure control, automatic
                                                        2
centering technique, 2D and 3D image post processing filters, noise projection software, statistical and
model based iterative reconstruction techniques, for CT radiation dose reduction. In addition, several of
his educational exhibits on CT radiation dose have been awarded with awards such as Magna Cum
Laude, Cum Laude, and Certificate of Merit. In addition, he has also presented on this subject
extensively as a faculty at the Radiological Society of North America’s Refresher Courses on CT
radiation dose, World Congress of Thoracic Imaging, American Society of Radiologic Technologists,
MGH-Harvard Medical School’s Annual Cardiac CT courses, and CT Radiation Dose Master Series
Course at the GE Healthcare Institute.

To perform further research on radiation dose reduction, the Center for Medical Image Sciences and
Visualization (CMIV) at the Linkoping University in Sweden has invited Dr. Kalra to serve as a visiting
professor for three months from January to April 2010. During his stay at the CMIV, Dr. Kalra will also
work with Dr. Anders Persson, Director of the CMIV, on several projects on virtopsy with both CT and
MRI. Dr. Persson, a scientific advisor for the virtopsy component for this proposal, is considered as one
of the pioneers in virtopsy. He has tremendous experience in both technical and interpretation
components of the virtopsy having done hundreds of these procedures personally. He has reported use
of dual energy CT and post mortem contrast enhanced angiography in post mortem settings. At the
MGH, Dr. Eugene Mark, Head of Autopsy Services for over 20 years, will serve as a scientific advisor
and partner from the pathologic correlation stand point of view.

• Project Plans:
Aim 1: To develop an educational program on CT radiation dose using CT data acquired at
multiple dose levels in deceased subjects who undergo conventional autopsy examination and
receive pathologic confirmation of lesions or abnormalities.
1A. Perform whole body CT scanning of 150 cadavers prior to their conventional autopsy at different
levels of radiation doses: The project will be performed following approval from our institutional review
board in compliance of the Human Insurance Portability and Accountability Act (HIPAA). We have
already obtained the permission of the MGH Autopsy Services for scanning subjects while they are
awaiting a post mortem examination. Once the body arrives in the autopsy section on the first floor of
the hospital (restricted access to hospital employee), Dr. Kalra and Dr. Vij will be paged. Bodies will be
then transferred into “zipper less” body bags that are artifact free for CT and MR imaging. The arms will
be positioned above the head if possible prior to placing the body into the body bag and a stretcher.
Special opaque case will be used to further hide the body on the stretcher prior to its transfer from the
autopsy section on the first floor of the hospital to the CT suite on the second floor (figure 1 in the
appendix). A restricted access elevator will be used in the autopsy section to move the cadaver to the
second floor corridor which leads to the CT suite on the same floor.

The body will be positioned in the CT gantry isocenter and scanned using following scanning
parameters: 120 kVp, 0.9:1 pitch, slice thickness 0.625mm, detector configuration 16*0.625 or
64*0.625mm, standard/detail/bone kernels, 0.5 second gantry rotation time. Tube current will be
adjusted to obtain 7 radiation dose levels for the subjects (400, 300, 200, 100, 50, 25, and 10 mAs).
These levels have been chosen to represent higher doses (at 400 and 300 mAs), routinely used levels
(200 and 100 mAs) and lower radiation doses (50, 25, 10 mAs). Once images are reconstructed both
the source raw data and images will be anonymized and exported to a password protected external
hard drive device with antivirus software.

1B. Create a web based educational software program for CT radiation dose training: We have written
an online program DoseTrainer (Copyright: MGH Enterprise Medical Imaging, Massachusetts General
Hospital Imaging) (Figure 2 in the appendix) using C# programming language (Microsoft Visual Studio
2005, Microsoft .NET 2.0 software framework, and data parsing, rendering and manipulation software
libraries of the LeadTools v15, with Microsoft Access 2003 for archiving diagnostic information). The
program allows the study participants to simultaneous review of 1 to 16 DICOM image series with on
high-resolution image workstations compliant with DICOM committee guidelines. The readers can
adjust window level and width, zoom in and out, pan images and enter comments tagged to each
image series. Currently, this program is installed on our standard PACS workstation used for diagnostic
                                                        3
reporting. However, our standard PACS image viewing monitors are only 24-28 inches in maximum
dimensions and hence would make images too small for simultaneous review of multiple image series.
Hence, we have specified a need for a wide screen high resolution monitor for simultaneous reviewing
of multiple image series using the DoseTrainer software. This high-resolution workstation will have
resolution and specifications identical to the workstations on which general clinical interpretation of CT
studies is performed. In order to create an online repository of low dose CT images, we will upload all
image series from the external hard drive to this internal web server based program (DoseTrainer). CT
examinations uploaded on this server will be accessible only with our hospital’s firewall for the duration
of the project. After completion of the project, external radiologists or institutions will be able to request
this de-identified data of low radiation dose for training purposes. We will only charge shipping and data
storage devices sent to the requesting or interested personnel. In order to monitor use and restrict
access to the study participants, access to the program will be available via specific username and
password with in the MGH intranet firewall.

We will take photographs of the pertinent autopsy findings at the time of the autopsy. These images will
be tagged to the DICOM image repository of each scanned subject. These mages will be useful as
standard of reference for the findings seen on CT images.

1C. Document baseline preferences of practicing and in training radiologists for image interpretation at
standard and different lower radiation dose levels: After creating a repository of about 50 subjects, we
will create a list of radiology residents (second, third or fourth year), fellows, and faculty who report CT
studies at the MGH. These personnel will be approached to volunteer for participation in this study.
Given the awareness and concerns over radiation dose and its risks, our conservative estimates
suggest that 50% of these personnel will agree to participate. We will use the following inclusion criteria
for the participating personnel: Willingness to review 40 CT studies from the image repository both at
the standard radiation dose and at the five different levels of reduced radiation dose; Willingness to
participate in the training phase and as well as re-evaluation of standard and low dose images as per
randomization; Agree to avoid discussion about the study with each other.

In this phase, all participants will be asked to review seven image datasets of 40 CT studies acquired
using above mentioned scanning parameters for number of lesions and their locations as well as
diagnostic acceptability and image noise. The seven datasets will be randomized and blinded for dose
levels. During this review, participants will be asked to comment on the image noise (graininess in the
image) and diagnostic acceptability of the CT for the given clinical indication. Diagnostic acceptability
will be assessed on the basis of prior studies on dose reduction and recommendations of the European
Guidelines on Quality Criteria for CT committee (EUR 16262) [Accessed on 12.17.2009 at
http://www.drs.dk/guidelines/ct/quality/mainindex.htm,]. Diagnostic confidence will be graded using the
following 4-point scale: 1, fully acceptable; 2, probably acceptable: 3, only acceptable in limited
conditions; and 4, unacceptable. Unacceptable diagnostic confidence is defined as completely
unsatisfactory visualization of these image attributes. Likewise, image noise will be graded on a 5-point
scale: 1, very little noise; 2, better than average noise; 3, acceptable noise; 4, more than acceptable
noise; and 5, too much noise. Image noise will be categorized as acceptable if there is average mottle
or graininess with acceptable visualization of anatomic structures and interfaces between structures of
different attenuation. Too much noise is defined as graininess or mottle that interfered with visualization
of these structures, and very little noise is graded on the basis of minimal image graininess.

1D. Train practicing and in training radiologists with low radiation dose CT images using CT
DoseTrainer program: After the assessment of baseline data, the study participants will be subdivided
into two groups. The intervention group will receive training with DoseTrainer program for visualization
of lesions at low radiation dose with 40 separate CT studies at different dose levels. To increase
attention and efficiency as well as to reduce reviewing time, only pertinent standard dose and
corresponding low dose images of each CT study will be shown. For training, the intervention group
participants will be shown each case at all seven dose levels (400, 300, 200, 100, 50, 25, 10 mAs). On
each image dataset, lesions, if any, will be labeled for them, so that they can recognize the appearance
of lesions at different levels of radiation dose. In addition, any artifacts, if any will also be marked to
                                                          4
train the participants. Participants will also be asked to record the diagnostic acceptability and image
noise for each image dataset as described above. According to our conservative experience, each
participant will need 9-12 hours for this training. To avoid reader fatigue and to accomplish quality
training, participants will be asked to review the images over a period of two months in at least three
sessions but not more than five sessions. Participants who fail to accomplish these goals will be either
excluded from the study or asked to start training from the beginning.
The non-intervention group will be shown same 40 labeled cases at highest dose level only (400 mAs).
They will also be asked to record the diagnostic acceptability and image noise for each case. Although
our estimates suggest that non-intervention participants should need no more than 5-6 hours to
complete review of these cases, goals set for intervention group will apply to this group as well. To
minimize bias and assess inter-observer variations, all participants of both groups will review cases
independently.

1E. Reevaluate post-training preferences for image interpretation at different lower radiation dose
levels: To assess the effect of the DoseTrainer program, with in four weeks of completing the training,
participants in both intervention and non-intervention groups will be again asked to evaluate 40
separate cases at seven different low radiation dose settings for number of lesions and their locations
as well as diagnostic acceptability and image noise. Once again, participants will be blinded to the
levels of radiation dose for randomized image datasets. This step will help us identify the effect of
training the practicing and in training radiologists at different levels of low radiation dose in terms of
their confidence and ability to detect findings.

Aim 2. Integration of pre-mortem and post mortem imaging studies and pathology services for
correlating radiologic images and autopsy findings for educational purposes
Radiologic pathology has long been regarded as an important aspect of radiology residency training
where in training radiologists learn about the “ground truth” of abnormalities seen on imaging studies.
Despite advances in medical imaging techniques, several studies highlight the fact there are major
discrepancies between the pre mortem diagnosis and actual postmortem pathology findings [38-45].
For example, in a recent retrospective study of cancer patients who died in the intensive care units in a
tertiary care center (between 1999 and 2005), Pastores et al reported that there was a 26%
discrepancy between premortem clinical diagnoses and postmortem findings found on autopsy [40].
Combes et al reported major diagnostic errors in almost one third of patients in a three-year prospective
clinical study between 1995 and 1998 on all consecutive autopsies performed on patients who died in a
university hospital medical and surgical intensive care units [41]. In another study, Burton et al found
44% discordance between clinical and autopsy diagnosis in patients with malignant neoplasms who
died at a large teaching hospital [42]. These studies suggest continued importance of conventional
autopsy in modern medicine as has also been emphasized in the Agency for HealthCare Research and
Quality (AHRQ), a division of the U.S. Department of Health and Human Services, report titled “The
Autopsy as an Outcome and Performance Measure” in 2002 [71]. The AHRQ report stated in about
11% of cases, autopsy is likely to reveal a major misdiagnosis that may have affected clinical outcome
(Class I error) in the United States and that only 25% of “Cause of Death” statements in death
certificates are correct [71]. Furthermore, recent studies have reported that virtopsy can add information
to the conventional autopsy and enhance the overall acceptability of limited autopsy examinations [45-
70].

2A. Perform CT and/or MRI in 150 cadavers prior to their conventional autopsy: The procedure for
performing the CT scanning has been described above. Only the highest dose CT images will be used
for the purposes of creating a virtopsy and conventional autopsy correlation presentations and program.
After whole body CT scanning, we will perform the MR virtopsy on a 1.5 Tesla scanner and acquire
axial, coronal and sagittal axial images with different contrast weighting (T1-weighted spin-echo and
T2-weighted fast spin-echo sequences with and without fat saturation, turbo inversion recovery
sequences, gradient-echo sequences) [55]. For cases with substantial expected or observed cardiac
abnormality, we will acquire targeted short-axis, horizontal long-axis, and vertical long-axis images of
the heart. All CT and MR images will be de-identified and transferred to an external hard drive. In
addition, we will also query our entire PACS network for any pre-mortem imaging examinations, which
                                                        5
will also be deidentified and transferred to the external hard drive. It is anticipated based on reported
literature that MRI of the whole body will take between 1 and 3 hours.

After exporting the images, we will interpret these images and document the findings in an electronic
format by body regions in a structured format as outlined below in table 1. In addition, medical records
of the subjects will be accessed to determine the antemortem diagnosis, and imaging tests available in
the hospital PACS. Pertinent ante-mortem imaging examinations will also be exported to the external
hard drive from the PACS workstations and will be used for correlation purposes.

2B. Photographic documentation of gross pathology specimens on conventional autopsy examination:
Following imaging, each cadaver will have a conventional autopsy. Each autopsy will be attended by
the study investigators (Dr. Kalra and/or Dr. Vij). All autopsy findings will be recorded in a structured
format similar to that described in table 1. Appropriate high definition photographs of the gross
pathology abnormality will be obtained. In addition, we will also obtain photomicrograph of pertinent
abnormality for which histological sections are performed.

2C. Create an online image archive of ante-mortem imaging (where available), virtopsy and
conventional autopsy image datasets: The above mentioned DoseTrainer program also allows
multimodality display of DICOM image data. We will use the program to create a radiologic autopsy
archive. The archive will allow simultaneous display of ante-mortem imaging tests, postmortem imaging
studies and conventional autopsy photographs along with the record of findings noted on each of the
three items. This archive will be used for presenting interesting cases each month during MGH lunch
hour noon conference as part of a new educational initiative named “virtopsy-autopsy correlation
conference.” Dr. Kalra or Dr. Vij will present the radiology findings and we will invite a pathologist to
discuss the conventional autopsy findings pertinent to the presented cases. In addition, the archive will
be made available for all MGH radiology personnel via the MGH resident intranet webpage link
(http:\\Reshub). This archive will allow the radiology fellows, residents and radiologists to view the
virtopsy and autopsy photographs with in the MGH firewall. All staff and in training radiologists will be
informed about timing of the conference and availability of the cases in the online archive via monthly
emails.

• Time Schedule:
Approval phase:
10.2009: Permission and willingness to perform virtopsy on subjects scheduled for conventional
autopsy obtained from the Chief of Autopsy Services as Mass General Hospital.
10.2009: Permission to perform CT of the cadavers scheduled for conventional autopsy upon approval
by the local ethical committee.
12.2009: Submission of documents to local ethical committee for approval of research
May 2010: Anticipated approval from Institutional Review Board
CT imaging data collection phase:
07.2010: Start date for CT virtopsy on subjects scheduled for conventional autopsy.
December 2011: End of data collection with scanning of 150 subjects
Creation of training program for radiologists and residents
11. 2010 to 12. 2011: Database creation for CT image quality and dose training software
11. 2010 to 12. 2011: Creation of radiologic and autopsy correlation educational materials
Launch of educational program
07.2011 to 06. 2012: Resident posting for virtopsy and conventional autopsy correlation: Anticipated
number of cases seen: 3-4 over three day period
07. 2011 to 06. 2012: Radiologist training for dose training and image quality assessment
Publications and presentations
Application of post mortem CT data for radiation dose reduction: RSNA 2011, 2012
Use of CT virtopsy for education of residents in radiologic-conventional autopsies: RSNA 2012
Report on survey of residents on use of virtopsy for educational purposes: RSNA 2012

• Outcomes:
                                                       6
Two main educational programs will be developed through this project. First and foremost, we will
develop an online software application (initially as an intranet web based program) using images from
the CT virtopsy to train the practicing and in training (residents and fellows) radiologists about effect of
low radiation dose on image quality and lesion characteristics. Secondly, another educational program
will be developed for antemortem and postmortem imaging correlation with autopsy findings. This
program will help in enhancing the understanding of expected imaging findings in human body following
death as well as findings contributing to or related to death while providing an imaging-pathology
correlation for these findings.

• Evaluation:
As outlined above effect of radiation dose training program will be assessed via change in diagnostic
confidence or preference of the participating radiologists for low dose CT images following training with
the DoseTrainer program. A blinded survey of radiologists will be performed at the end of the
DoseTrainer program in order to determine their satisfaction with the program as well as suggestions
for improving the training program. Likewise, we will perform a blinded survey of the attendees of the
monthly virtopsy - autopsy conferences to assess their feedback about the presented materials. We will
also monitor the “hit rates” for different cases of these conferences uploaded on our local intranet site.



_________________________END OF THE PROPOSAL____________________________

                       Section below is an appendix to the main document




                                                         7
APPENDIX
 Figure 1. Proposed route of travel from the autopsy services area (first floor) to the CT suite
 (second floor of the same building). Both the autopsy area and CT suites are restricted areas.




 Figure 2. Diagramatic representation of the proposed CT DoseTrainer for our proposed project. The
 interface allows zooming, scrolling through multiple series, panning, adjusting windows, and
 taking notes and entering image quality scores.




                                                        8
   Table 1. Structured interpretation and record of the findings noted. For each abnormality, we will
   record the size, exact location and perceived diagnosis.
         Brain               Face and neck       Chest               Abdomen/pelvis      Extremities
         Ventricles          Salivary glands     Lungs               Liver               Bones
         Sulci               Aero-digestive      Pleura              Gall bladder        Muscles
         Parenchyma          Thyroid gland       Heart               Biliary tract       Joints
         - Supratentortial   Other soft tissue   Pericardium         Spleen              Blood vessels
         - Infratentorial    Neck vessels        Blood vessels       Pancreas            Other soft tissue
         Blood vessels       Sinuses             Esophagus           Kidneys
         Skull               Cervical spine      Axilla              Ureters/ Bladder
         Scalp                                   Other soft tissue   Adrenals
                                                 Bony thorax         GI tract
                                                                     Other soft tissue
                                                                     Blood vessels
                                                                     Reproductive
                                                                     Bones


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