Liver ablation monitoring with ultrasound elastography
Summer Studentship Project at the Department of Surgery
Supervisors
Sulaiman Nanji, MD, FRCSC (nanjis@KGH.KARI.NET)
Assistant Professor, Department of Surgery
Gabor Fichtinger, PhD (fichting@queensu.ca)
Professor and Cancer Care Ontario Research Chair
School of Computing
Suitability for 1st or 2nd year medical students
This project is suitable for 1st and 2nd year medical students.
Funding
This is a new multidisciplinary collaboration between the Department of Surgery and the School
of Computing. The project does not yet have independent grant funding and one of the project
objectives is to generate preliminary results to support a NSERC CHRP research grant proposal to
be submitted in October, 2014.
We propose the following cost matching scenario. For the medical student, we seek 100%
funding from the Summer Studentship Program. The medical student will work in tandem with
an engineering graduate research assistant. The RA will handle surgical navigation and ultrasound
imaging instrumentation and is funded from Cancer Care Ontario Research Chair and Applied
Cancer Research Unit Grants of the supervisors.
Supervisors
Sulaiman Nanji, MD, FRCSC, Department of Surgery, nanjis@KGH.KARI.NET
Gabor Fichtinger, PhD, School of Computing, fichting@queensu.ca
Department
Department of Surgery
Contact
Sulaiman Nanji, MD, FRCSC (nanjis@KGH.KARI.NET)
Gabor Fichtinger, PhD (fichting@queensu.ca)
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Project Description
Background: Liver cancers, either primary or metastatic, represent a significant source of
morbidity and mortality. Hepatocellular carcinoma is a primary malignancy of the liver and is one
of the most common cancers in the world, with an annual incidence of at least 1 million new
patients. Metastatic disease to the liver, primarily from colorectal cancer, is the most frequent
hepatic malignancy in the United States and Canada. The survival rate for untreated patients with
of both these diseases is dismal. Despite recent advances in cancer therapy, treatment of primary
and metastatic tumors of the liver remains a significant challenge to the health care community
worldwide. The principal potentially curative treatment for these patients is liver resection,
resulting in 5-year survival rates between 25 and 55%. Unfortunately, only approximately 10-20%
of patients with either primary or metastatic liver disease are candidates for surgical resection.
In addition, patients with technically resectable tumours may not be candidates for surgery due
to severe hepatic dysfunction precluding resection. Therefore, minimally invasive treatment of
liver cancer has become an area of considerable interest. Specifically, interstitial ablative
approaches for the treatment of unresectable liver tumors is gaining widespread interest. In
addition to increasing the number of patients eligible for curative therapy of liver cancer, local
tissue ablation is performed with lower morbidity than resection, and can often be combined
with resection for multiple tumours.
Liver radiofrequency ablation in open surgical setting with intra-operative ultrasound guidance (left) and
intra-operative ultrasound image of the target cancer (right).
A variety of methods have been employed to locally ablate tissue. Thermal ablation using
radiofrequency energy is the most frequently used modality. Other ablative modalities employ
thermal destruction as well, including microwave, laser coagulation, and high-frequency
ultrasound. Less commonly used techniques employ other methods to destroy tissue, including
cold (cryotherapy) and chemical means (ethanol and acetic acid). Radiofrequency ablation (RFA)
is an interstitial focal ablative therapy in which an electrode is placed into a liver lesion to cause
tissue heating from ionic agitation, resulting in heating and cauterization of the tumor mass and
probe track. RFA devices are of generally 15-18 gauge and can be used in a percutaneous fashion,
with minimal risk of bleeding. The heat created around the electrode is subsequently conducted
into the surrounding tissue in a predictable manner, causing coagulative necrosis at a
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temperature between 50°C and 100°C. The size of the ablated area is determined largely by the
current’s intensity and length, the gauge of the electrode tip, and the duration of energy applied.
The current intensity that can be used is limited by tissue carbonization around the needle tip,
which can result in a sharp rise in tissue impedance and thus interruption of the radiofrequency
wave flow. This effectively limits the area of tissue that can be ablated by a single probe. Tissue
vascularization is also an important factor that determines the volume of tissue ablated.
Complete necrosis of highly vascular tumors or tumors adjacent to large vessels may be impeded
by the cooling effect of blood flow. Owing to recent advances in RFA device technology, it is
possible to ablate tumors up to 5 cm in diameter, which has ignited new enthusiasm for RFA in
liver cancer management.
One common feature of current thermal ablative methodology is the necessity for precise
assessment of the zone of tissue destruction. This zone needs to typically encompass the tumor
and an approximately 1 cm safety margin in the surrounding normal liver parenchyma, without
causing destruction of vital structures in potential proximity to the ablation zone. Tumors are
identified by preoperative imaging, primarily CT and MR, and then operatively localized by
intraoperative ultrasonography. Typically, the RFA process is guided and monitored using
ultrasonography, followed by definitive CT and/or MR imaging some time after the procedure to
assess the zone of ablation. Sonography has the advantage of being readily and widely available,
is an excellent real-time imaging technique for probe placement, and is a reasonably good
technique for visualizing hepatic tumors. However, during the ablation, artifacts created by
thermal tissue changes and the low contrast resolution of ultrasonography limits the ability of
ultrasonography to precisely visualize the extent of necrosis and can severely hinder the ability
to accurately determine the area of ablation during the procedure, leading to overtreatment of
some previously ablated areas and undertreatment of others. It is generally acknowledged that
the lack of concordance between imaging findings during the procedure and actual tissue
ablation is responsible for many of the local tumor recurrences after RFA therapy.
There is potential for improving on ultrasound imaging by a quantitative measure of tissue
elasticity imaging. This approach takes advantage of changes in tissue biomechanical
characteristics caused by coagulation during tissue ablation. In ultrasound elastography imaging,
the subject tissue is imaged in both slightly compressed and uncompressed state and the images
are compared and “subtracted” to generate strain images reflecting relative differences in tissue
elasticity. During the past decade, elastography imaging went through major development. It is
now possible to discriminate stiff versus normal tissue to a minute level, such as differentiating
breast tumors from normal breast tissue. Elastography has become a feature available on several
ultrasound systems today.
Intraoperative ultrasound in the open surgical setting (see Figure) offers the potential for
ultrasound elastography imaging through exerting the required tissue compression by pressing
the ultrasound transducer against the liver tissue and then releasing it from pressure. There are
many unknown factors of this technique; it is not known how exactly to compress and relax the
tissue and how the ultrasound acquisition parameters should be set. There has been no clinical
study that would describe the workflow and knowhow of ultrasound elastography in open liver
surgery setting. The purpose of this project to fill in this gap.
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Project Objectives:
(1) Develop a clinically practical workflow for utilizing ultrasound elastography imaging in
targeting and monitoring the liver ablation process in an open surgical setting.
(2) Demonstrate the robustness, accuracy and consistency of this method in a laboratory
setting using an ex-vivo animal model.
Job Responsibilities: The student, working side by side an experienced engineering graduate
research assistant, will take part in the following activities: Development of clinical workflow for
US-guided liver ablation and monitoring; Design of experimental laboratory workflow; Design exvivo tissue procurement, preparation, and evaluation protocol; Execute the ex-vivo animal tissue
experiments; Evaluate results pathologically; Write research reports and publications; Contribute
to writing research grant proposals.
Learning Objectives: Learn the fundamentals of image-guided computer-assisted surgery and
surgical navigation and component technologies. Learn the anatomy of the liver. Learn the
fundamentals of liver cancer ablation in an open surgical setting. Learn the fundamentals of
ultrasound elastography and operation of ultrasound scanners. Learn tissue preparation for exvivo experiments. Learn pathological examination of samples, post operatively. Learn the basics
of biostatistics in practice by analyzing collected data during ex-vivo surgery sessions. Learn to
work in a collaborative integrated commercial-quality system development environment. Learn
to write scientific publications. Over the past several years, the Perk Lab has advised dozens of
undergraduates and medical students. Some have first-authored refereed international
publications, while others have contributed to publications as co-authors. Our summer trainees
have received numerous research awards and fellowships as a direct result of their research work
in the Perk Lab. We will uphold this high academic standard and help our new summer trainees
to be similarly successful and productive.
Performance Site: The student will first observe liver surgeries and ablations in the operating
theater as performed by Dr. Nanji. Following an intensive introduction to the clinical context, the
student will conduct a series of experiments in the Laboratory for Percutaneous Surgery (Perk
Lab, http://perk.cs.queensu.ca) where office and experimental space will be available. The Perk
Lab has been equipped from recent infrastructure grants (1 million dollars combined), providing
state-of-the-art computers, software, position and motion tracking devices, needle placement
surgery robots, virtual reality surgical guidance systems, a motorized C-arm fluoroscope,
ultrasound scanners with open research interface to beam-former and radiofrequency stream,
ultrasound transducers, focused ultrasound tissue ablation system with open research interface,
and appropriate interface appliances needed for integrated surgical robotics and navigation
systems. The Perk Lab is home to over 20 researchers (students, postdocs and research
scientists). Uniquely among academic faculty laboratories, the Perk Lab employs professional
medical systems engineers hired from industry. Their role is to support academic research by
integrating and maintaining software and systems, in order to sustain long-term research
programs over generations of trainees.
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Student Qualifications: The student must have completed one or more years in medical school,
with basic knowledge of anatomy, pathology and physiology. Experience with preparing,
handling, and processing ex-vivo tissue samples is necessary. Ideally, the student should also be
familiar with the basics of computer-assisted surgery and ultrasound imaging. (The student will
have to obtain health clearance for observing surgeries in the operating theater.)
Application Process: Applicants should directly contact the supervisors via email, with attaching
a brief cover letter, CV and relevant materials, such as transcripts, reprints of prior research
publications, project reports, etc.
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