CT, MRI, Ultrasound & PET Comparison for Hepatic Malignancy Study

This study investigates the effectiveness of CT, MR Imaging, Ultrasound, and PET in detecting primary hepatic malignancy (HCC) in liver transplant patients. The research employs a descriptive design and simple random sampling, involving 25 patients undergoing these tests, with data analyzed by two radiologists. The aim is to determine the most accurate diagnostic technique for HCC or CCA, considering factors like hepatic function and tumor grade. The study assesses diagnostic performance, interobserver variability, and potential clinical value, particularly noting the limited utility of FDG PET in patients with weak hepatic function and the association between FDG uptake and tumor grade. Data collection includes primary and secondary sources, with numerical experiment procedures and computational techniques used for signal and image processing. The research aims to provide useful implications for medical practitioners in selecting the most effective technique for HCC detection prior to liver transplantation.

Running head: DETECTION OF PRIMARY HEPATIC MALIGNACY
Study Developing Detection of Primary Hepatic Malignancy in Liver Transplant Patient:
Prospective Comparison of CT, MR Imaging, Ultrasound and PET
Name of the University:
Name of the Student:
Authors Note:

1DETECTION OF PRIMARY HEPATIC MALIGNACY
Abstract
It is considered important to undergo screening for the patients having Hepatocellular Carcinoma
(HCC) likely to undergo liver transplant. The significance of the current research is to offer
useful implications to the medical practitioners regarding the most effective technique used in
determining the HCC presence in the patients that are considered to undergo a liver transplant
process. In analysing the effectiveness of CT, MR Imaging, Ultrasound and PET for successful
detection of HCC among the liver transplant patients, 25 patients will be selected in the survey
that will undergo such tests and 2 radiologists.The data will be analysed on a patient-by-patient
basis with marginal homogeneity along with ratio tests on effect likelihood. The results of the
study is also estimated to suggest that the patients having weak hepatic function, FDG PET is of
very less clinical value for the detection of HCC. In addition, FDG uptake degree in HCCs is
indicated to be associated with tumour grade.

2DETECTION OF PRIMARY HEPATIC MALIGNACY
Table of Contents
1. Introduction..................................................................................................................................3
1.1. Background and Literature Review......................................................................................3
1.2. Significance of Proposed Research......................................................................................4
1.3. Purposes................................................................................................................................5
1.4. Research Aim, Questions and Objectives.............................................................................6
2. Research Methods and Designs...................................................................................................7
2.1. Research Design...................................................................................................................7
2.2. Sampling and Sample Size...................................................................................................8
2.3. Preparatory Methods.............................................................................................................9
2.4. Data Collection Method........................................................................................................9
2.5. Data Analysis Method........................................................................................................10
2.6. Ethical Considerations........................................................................................................12
7. Time Schedule and Budget........................................................................................................12
8. Outcomes...................................................................................................................................14
References......................................................................................................................................16

3DETECTION OF PRIMARY HEPATIC MALIGNACY
1. Introduction
1.1. Background and Literature Review
The importance of orthotic transplantation of liver in successfully rating the patents
dealing ith end stage Hepatocellular Carcinoma (HCC) have been researched by numerous
previous reasechers. It was reported that long-term survival can be attained through successful
liver transplantation among these patients that are observed to have solitary 5cm or smaller
Hepatocellular Carcinoma (HCC) or have tumor nodules smaller than 3cm in diameter. In
addition, patients having cholangio carcinoma (CCA) that has already undergone liver
transplantation was observed to face a poor outcome due to tumor recurrence. For this reason, it
is considered important to undergo screening for the patients having Hepatocellular Carcinoma
(HCC) likely to undergo liver transplant. This can facilitate in determining the eligibility for such
transplant particularly in consideration to shortage of donor livers.
Previous researches carried out by 1indicated regarding accuracy of certain individual or
combination of tests in successful diagnosis of Hepatocellular Carcinoma (HCC). These
researches have also revealed that tests including CT and MR imaging served as most effective
tools in HCC detection. However, later studies such as indicated poorer results specifically when
large population size was examined. This research also considered carrying out comparative
1 Castilla-Lièvre, M, D Franco, P Gervais, B Kuhnast, H Agostini, & L Marthey et al.,
"Diagnostic value of combining 11C-choline and 18F-FDG PET/CT in hepatocellular
carcinoma.". in European Journal of Nuclear Medicine and Molecular Imaging, 43, 2015, 852-
859.

4DETECTION OF PRIMARY HEPATIC MALIGNACY
study regarding accuracy of combination of CT and US tests in better HCC detection and
reported varying findings. Most of the previous researches were retrospective and the finding on
imaging was not compared with the findings of liver explanation. In a recent study carried out
by 2it was revealed that PET with FDG has turned out to have a significant role in helping to
detect as well as stage some type of cancers. In addition these study findings have also revealed
that FDG PET is moderately sensitive in successful CCAA determination. 3added that use of
FDG PET in determination of primary hepatic tumors among the patients those are to undergo
liver transplantation and have weaker hepatic function was not yet researched. Moreover,
focused on such findings the current research will be focused on comparing diagnostic
performance of CT, MR imaging, US and PET against histological examination standard of
respected liver specimen in order to estimate the most suitable test in accurate detection of CCA
or HCC in selected liver transplant patients.
1.2. Significance of Proposed Research
The significance of the current research is to offer useful implications to the medical
practitioners regarding the most effective technique used in determining the HCC presence in the
patients that are considered to undergo a liver transplant process. Moreover, constructive
findings will be gathered in the research regarding the fact that hepatic imaging is generally
2 Ehman, E, S Thompson, B Welch, D Johnson, & H McGregor, "PET Imaging of Hepatocellular
Carcinoma.". in Current Radiology Reports, 7, 2019.
3 Deppen, S, E Liu, J Blume, J Clanton, C Shi, & L Jones-Jackson et al., "Safety and Efficacy of
68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of
Neuroendocrine Tumors.". in Journal of Nuclear Medicine, 57, 2016, 708-714.

5DETECTION OF PRIMARY HEPATIC MALIGNACY
carried out in revealing primary or metastatic liver disease4. It will also offer significant analysis
on the fact whether CT can serve as the initial diagnostic test for most indications because of its
availability, versatility, specificity and increased sensitivity. Moreover, the research will also be
carried out through employing most appropriate research methods and design that can provide
useful findings on comparing their MRI is effective than CT in detection of lesion and whether it
can be implemented in cases where CT is non-contributory5.
1.3. Purposes
The purpose of the current research is to evaluate and compare the diagnostic
performance of magnetic resonance (MR) imaging, computed tomography (CT), Ultra
sonography (US) as well as positron emission tomography (PET) in effective detection of HCC
in the patients of liver transplant and also to determine the intra observer variability among the
readers. The research will also focus on analyzing whether US attains the best diagnostic
performance on successful HCC depiction based on the patient-to-patient approach. Moreover,
this research will also be focused on explaining the selection of imaging test will greatly rely on
the availability, clinical question, and familiarity of the clinicians with the test as well as clinical
4 Flechsig, P, C Zechmann, J Schreiweis, C Kratochwil, D Rath, & L Schwartz et al.,
"Qualitative and quantitative image analysis of CT and MR imaging in patients with
neuroendocrine liver metastases in comparison to 68 Ga-DOTATOC PET.". in European
Journal of Radiology, 84, 2015, 1593-1600.
5 Fraum, T, D Ludwig, T Hope, & K Fowler, "PET/MRI for Gastrointestinal Imaging.". in
Gastroenterology Clinics of North America, 47, 2018, 691-714.

6DETECTION OF PRIMARY HEPATIC MALIGNACY
conditions of the patients6. The purpose of this study is also to evaluate that the technique of US
and CT are considered as the first imaging tests in screening as well as charactering most of the
patients that are suspected to have tumors in livers.
1.4. Research Aim, Questions and Objectives
The aim of the research is to “Study Developing Detection of Primary Hepatic
Malignancy in Liver Transplant Patient: Prospective Comparison of CT, MR Imaging,
Ultrasound and PET”. Focused on such aim the objectives that are to be met through completion
of the current research are indicated below:
 To analyze and compare the diagnostic performance of magnetic resonance (MR)
imaging, computed tomography (CT), Ultra sonography (US) as well as positron
emission tomography (PET)
 To evaluate the effectiveness of MR, CT, US and PET in successful detection of
Hepatocellular Carcinoma (HCC) among the patients of liver transplant
 To determine the interobserver variability through examining presence and type of lesion
The research questions that are to be answered through attainment of the study are indicated
under:
6 Kesler, M, C Levine, D Hershkovitz, E Mishani, Y Menachem, & H Lerman et al., "68Ga-
Labeled Prostate-Specific Membrane Antigen Is a Novel PET/CT Tracer for Imaging of
Hepatocellular Carcinoma: A Prospective Pilot Study.". in Journal of Nuclear Medicine, 60,
2018, 185-191.

7DETECTION OF PRIMARY HEPATIC MALIGNACY
 What are the ways to analyze and compare the diagnostic performance of magnetic
resonance (MR) imaging, computed tomography (CT), Ultra sonography (US) as well as
positron emission tomography (PET)?
 What are the ways to evaluate the effectiveness of MR, CT, US and PET in successful
detection of Hepatocellular Carcinoma (HCC) among the patients of liver transplant?
 How to determine the interobserver variability through examining presence and type of
lesion?
2. Research Methods and Designs
2.1. Research Design
In carrying out this research, descriptive research design will be selected for the reason
that it can facilitate the researcher in revealing and defining the major issues related with subject
of research7. Moreover, this research deign is suitable as it can also facilitate in offer the
researcher with an opportunity to broaden the understanding and the knowledge base. As the
study deals with analysing the most suitable test technique among CT, MR Imaging, Ultrasound
and PET in detection of HCC among liver transplant patients descriptive research design can
facilitate in revealing the issues faced on carrying out each test while detecting HCC along with
developing a list of recommendations in addressing revealed issue8.
7 Lee, S, & S Kim, "Role of positron emission tomography/computed tomography in living
donor liver transplantation for hepatocellular carcinoma.". in HepatoBiliary Surgery and
Nutrition, 5, 2016, 408-414.
8 Lee, Y, J Lee, J Lee, H Lee, B Park, & Y Kim et al., "Hepatocellular Carcinoma: Diagnostic
Performance of Multidetector CT and MR Imaging—A Systematic Review and Meta-Analysis.".

8DETECTION OF PRIMARY HEPATIC MALIGNACY
2.2. Sampling and Sample Size
For selecting the target respondents on the research, simple random sampling technique
will be used as it offers equal chances to all the respondents from target population to get
selected for the survey. In analysing the effectiveness of CT, MR Imaging, Ultrasound and PET
for successful detection of HCC among the liver transplant patients, 25 radiologists will be
selected in the survey that will carry out such tests on the patients. Each of the test results will be
independently examined by the radiologists and then they will answer the survey questions9.
These target radiologists will be selected as they are the most suitable individuals that can
answer survey questions after carrying out tests on the patients. These individuals will be most
suitable people to answer the relevant survey questions on patients explanted over specimens
along with presence and type of liaison10.
in Radiology, 275, 2015, 97-109.
9 Lu, W, S Li, J Li, J Wang, R Zhang, & Y Zhou et al., "Effects of Omega-3 Fatty Acid in
Nonalcoholic Fatty Liver Disease: A Meta-Analysis.". in Gastroenterology Research and
Practice, 2016, 2016, 1-11.
10 Marion-Audibert, A, M Vullierme, M Ronot, J Mabrut, A Sauvanet, & M Zins et al., "Routine
MRI With DWI Sequences to Detect Liver Metastases in Patients With Potentially Resectable
Pancreatic Ductal Carcinoma and Normal Liver CT: A Prospective Multicenter Study.". in
American Journal of Roentgenology, 211, 2018, W217-W225.

9DETECTION OF PRIMARY HEPATIC MALIGNACY
2.3. Preparatory Methods
Numerical experiment procedure will be explained in the study and the settings of the
numerical experiment will be used in investigating the signal as well as the image processing
techniques of all the considered techniques such as CT, MR Imaging, Ultrasound and PET.
These testing techniques will be used in through following a three-dimensional imagining
diagnosis method in which the flow analysis of liver having HCC can be explained in a detailed
manner. In addition, the preparatory methods that will be employed in the current research will
be computational techniques in which all the measurement and computation will entail a system
of simulation on the basis of concept regarding HCC detection11.
2.4. Data Collection Method
For carrying out research on “Study Developing Detection of Primary Hepatic
Malignancy in Liver Transplant Patient: Prospective Comparison of CT, MR Imaging,
Ultrasound and PET“the relevant data will be gathered from both the primary and secondary
sources. The secondary sources will include previous peer reviewed journals, books and existing
as well as previous liver transplant patient records that will include data on their previous tests on
liver and the treatment they are going through12. The primary data will be gathered through
11 Oliveira, I, A Kilcoyne, J Everett, M Mino-Kenudson, M Harisinghani, & K Ganesan,
"Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management.". in
Abdominal Radiology, 42, 2017, 1637-1649.
12 Ronot, M, A Clift, V Vilgrain, & A Frilling, "Functional imaging in liver tumours.". in Journal
of Hepatology, 65, 2016, 1017-1030.

10DETECTION OF PRIMARY HEPATIC MALIGNACY
questionnaire survey technique that in which relevant questions regarding the study subject will
be asked to the selected patients and the radiologist observers. Data will be gathered on the test
results that will be undergone by the selected patients including CT, MR Imaging, Ultrasound
and PETfor detection of their HCC. Such primary data gathered will be used for quantitative
analysis in which the numeric data gathered will be used for carrying out valid analysis. The
questionnaire will be prepared on a likert scale basis for gathered numerical responses on a rating
scale of 1 to 5 and will be sent to the target patients and selected radiologist through personalised
e-mails where a timeframe of seven days will be provided for reverting on the questionnaire.
2.5. Data Analysis Method
Following the schematic diagram of simulation indicated in the figure below the data
gathered will be analysed through employing most specific and reliable statistical analytical
techniques. The data will be analysed on a patient-by-patient basis with marginal homogeneity
along with ratio tests on effect likelihood. In the patient based analysis technique there will be
agreement between the two selected observers for each imaging technique will be measured with
the k statistic. Differences between the paired and the ordinal responses represented by the
observers for the similar method will also be tested for statistical significance with tests n
marginal homogeneity. The gathered data will be represented in the form of tables for simple
data findings interpretation13. The simulated data will be used for analysis where sensitivity
analysis will be carried out considering sensitivity will include proportion of all the patients with
13 Ronot, M, A Clift, V Vilgrain, & A Frilling, "Functional imaging in liver tumours.". in Journal
of Hepatology, 65, 2016, 1017-1030.

11DETECTION OF PRIMARY HEPATIC MALIGNACY
the disease that will indeed have a positive test results as reported by the radiologists within the
survey findings.
Figure 1: Schematic Diagram of Simulation
(Source: Authors Creation)
2.6. Ethical Considerations
In carrying out the current research the researcher will ensure that all the ethical codes of
conduct will be followed in its completion. While surveying the target respondents it will be
ensured that mutual concerns attained from the patients before they are persuaded to take part in
the survey. In addition, for sanctuary reasons, the researcher will also ensure that the
confidentiality of the patients’ identity and privacy of the data gathered will be maintained

12DETECTION OF PRIMARY HEPATIC MALIGNACY
through not disclosing them14. It will also be ensured that use of gathered data will only be for
research purposes and no business use of the information will be entertained. The researcher will
also consider respecting along with safeguarding the rights of free will, confidentiality and
privacy of the participant radiologists along with decreasing the burden of study participation
that is possible at a great extent. The researcher will also consider abiding by the ethical as well
as legal obligations towards the survey participants.
7. Time Schedule and Budget
Activities 1st to
3rd Week
4th
to 10th
week
1
1th to
13th
Wee
k
14th to
17th Week
18t
h to
21st
Week
22nd
to 23rd
Week
24th
Week
Selection of the topic 
Data collection from
secondary sources
 
Creating layout 
Literature review   
Analysis and
interpretation of
  
14 Santambrogio, R, C Cigala, M Barabino, M Maggioni, G Scifo, & S Bruno et al.,
"Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour:
Prospective comparison with pathology.". in Liver International, 38, 2017, 312-320.

13DETECTION OF PRIMARY HEPATIC MALIGNACY
collected data
Findings of the data  
Conclusion of the
study

Formation of draft  
Submission of final
work

Particulars (Budget for Research) Expenditure
Postage 180
Travel 100
Overheads 200
Miscellaneous 190
Total 670
The budget for carrying out the research is indicated in the table above that will include
expenses for using research equipments such as access to internet connection, stationeries,
printing devices and travel costs. No cost will be experienced in the survey process as the
questionnaire will be delivered to the participant radiologists through online delivery by means
of free university account.
8. Outcomes
Completion of the research on the selected subject is intended to reveal the following
significant findings or outcomes:

14DETECTION OF PRIMARY HEPATIC MALIGNACY
 PET is anticipated to demonstrate heterogeneous as well as relatively poor FDG
accumulation within the liver in all the target patients participated within the study. Such
findings are anticipated to signify weak hepatic function along with distortion of hepatic
structure within the population of this study15.
 The results of the study is also estimated to suggest that the patients having weak hepatic
function, FDG PET is of very less clinical value for the detection of HCC. In addition,
FDG uptake degree in HCCs is indicated to be associated with tumour grade16.
 The findings will also reveal that the atrial phase dynamic imaging of MR is more than
helical CT in detection of smaller HCCs. In addition, it will also reveal that maximum
lesions that were missed with the tests carried out remains 2cm or even smaller17.
15 Teefey, S, C Hildeboldt, F Dehdashti, B Siegel, M Peters, & J Heiken et al., "Detection of
Primary Hepatic Malignancy in Liver Transplant Candidates: Prospective Comparison of CT,
MR Imaging, US, and PET.". in Radiology, 226, 2003, 533-542.
16 Wu, X, J Li, C Wang, G Zhang, N Zheng, & X Wang, "Application of Different Imaging
Methods in the Early Diagnosis of Primary Hepatic Carcinoma.". in Gastroenterology Research
and Practice, 2016, 2016, 1-7.
17 Wu, X, J Li, F Zhang, N Zheng, & X Wang, " Different Imaging Methods in the Early
Diagnosis of Primary Hepatic Carcinoma.". in Gastroenterology Research and Practice, 2016,
2016, 1-7.

15DETECTION OF PRIMARY HEPATIC MALIGNACY
References
Castilla-Lièvre, M, D Franco, P Gervais, B Kuhnast, H Agostini, & L Marthey et al., "Diagnostic
value of combining 11C-choline and 18F-FDG PET/CT in hepatocellular carcinoma.". in
European Journal of Nuclear Medicine and Molecular Imaging, 43, 2015, 852-859.
Deppen, S, E Liu, J Blume, J Clanton, C Shi, & L Jones-Jackson et al., "Safety and Efficacy of
68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of
Neuroendocrine Tumors.". in Journal of Nuclear Medicine, 57, 2016, 708-714.
Ehman, E, S Thompson, B Welch, D Johnson, & H McGregor, "PET Imaging of Hepatocellular
Carcinoma.". in Current Radiology Reports, 7, 2019.
Flechsig, P, C Zechmann, J Schreiweis, C Kratochwil, D Rath, & L Schwartz et al., "Qualitative
and quantitative image analysis of CT and MR imaging in patients with neuroendocrine liver
metastases in comparison to 68 Ga-DOTATOC PET.". in European Journal of Radiology, 84,
2015, 1593-1600.
Fraum, T, D Ludwig, T Hope, & K Fowler, "PET/MRI for Gastrointestinal Imaging.". in
Gastroenterology Clinics of North America, 47, 2018, 691-714.
Kesler, M, C Levine, D Hershkovitz, E Mishani, Y Menachem, & H Lerman et al., "68Ga-
Labeled Prostate-Specific Membrane Antigen Is a Novel PET/CT Tracer for Imaging of
Hepatocellular Carcinoma: A Prospective Pilot Study.". in Journal of Nuclear Medicine, 60,
2018, 185-191.

16DETECTION OF PRIMARY HEPATIC MALIGNACY
Lee, S, & S Kim, "Role of positron emission tomography/computed tomography in living donor
liver transplantation for hepatocellular carcinoma.". in HepatoBiliary Surgery and Nutrition, 5,
2016, 408-414.
Lee, Y, J Lee, J Lee, H Lee, B Park, & Y Kim et al., "Hepatocellular Carcinoma: Diagnostic
Performance of Multidetector CT and MR Imaging—A Systematic Review and Meta-Analysis.".
in Radiology, 275, 2015, 97-109.
Lu, W, S Li, J Li, J Wang, R Zhang, & Y Zhou et al., "Effects of Omega-3 Fatty Acid in
Nonalcoholic Fatty Liver Disease: A Meta-Analysis.". in Gastroenterology Research and
Practice, 2016, 2016, 1-11.
Marion-Audibert, A, M Vullierme, M Ronot, J Mabrut, A Sauvanet, & M Zins et al., "Routine
MRI With DWI Sequences to Detect Liver Metastases in Patients With Potentially Resectable
Pancreatic Ductal Carcinoma and Normal Liver CT: A Prospective Multicenter Study.". in
American Journal of Roentgenology, 211, 2018, W217-W225.
Oliveira, I, A Kilcoyne, J Everett, M Mino-Kenudson, M Harisinghani, & K Ganesan,
"Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management.". in
Abdominal Radiology, 42, 2017, 1637-1649.
Ronot, M, A Clift, V Vilgrain, & A Frilling, "Functional imaging in liver tumours.". in Journal
of Hepatology, 65, 2016, 1017-1030.
Santambrogio, R, C Cigala, M Barabino, M Maggioni, G Scifo, & S Bruno et al., "Intraoperative
ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective
comparison with pathology.". in Liver International, 38, 2017, 312-320.

17DETECTION OF PRIMARY HEPATIC MALIGNACY
Teefey, S, C Hildeboldt, F Dehdashti, B Siegel, M Peters, & J Heiken et al., "Detection of
Primary Hepatic Malignancy in Liver Transplant Candidates: Prospective Comparison of CT,
MR Imaging, US, and PET.". in Radiology, 226, 2003, 533-542.
Wu, X, J Li, C Wang, G Zhang, N Zheng, & X Wang, "Application of Different Imaging
Methods in the Early Diagnosis of Primary Hepatic Carcinoma.". in Gastroenterology Research
and Practice, 2016, 2016, 1-7.
Wu, X, J Li, F Zhang, N Zheng, & X Wang, " Different Imaging Methods in the Early Diagnosis
of Primary Hepatic Carcinoma.". in Gastroenterology Research and Practice, 2016, 2016, 1-7.