TOTAL LIVER VOLUME CT PERFUSION AFTER AUTOMATED 3D IMAGE FUSION: A NOVEL IMAGING TECHNIQUE FOR EARLY DETECTION OF OCCULT COLORECTAL LIVER METASTASES AND IMPROVED VISUALIZATION OF LOCAL TUMOR EXTENT IN PATIENTS WITH COLORECTAL LIVER METASTASES

Introduction & purpose
The visualization of typical hypodense colorectal liver metastases on
portovenous phase CT images is often preceeded by a hyperdense blush on
arterial phase CT. This is a direct result of the increased peritumoural
angiogenesis surrounding an occult liver metastasis due to the local elevation
of cytokines such as vascular endothelial growth factor (VEGF). Dynamic
perfusion CT has previously shown to detect liver metastases in an earlier
stage, especially due to an elevated microvessel density surrounding the occult
metastases which leads to increased perfusion values [1]. However at the moment
conventional CT perfusion is restricted to the evaluation of 2 * 3cm of axial
slice thickness through the liver [2, 3]. Conventional portovenous phase CT
images only show the hypodense (partially) necrotic regions of the liver
lesions, whereas CTP also depicts the highly angiogenetic rim of the liver
metastases [4]. Therefore, although it is unclear whether it represents
reactive liver parenchyma or true tumour tissue, CTP might better delineate the
true local tumor extent into the surrounding tissues. The purpose of this study
is to compare routine multiphase (4-phase) CT images of the liver with
ultra-fast total volume multiphase (12-phase) dynamic CTP of the liver for the
detection of small and occult liver metastases and for local tumour extent,
using automated 3D image fusion, taking the intraoperative inspection and
ultrasound, performed maximum 24 hours after the scan, as the gold standard. A
secondary goal will be the correlation with histology (after surgical resection
of liver lesions) in which we hope to determine whether the rim of high
arterial perfusion surrounding liver metastases represents reactive normal
liver parenchyma or true tumour tissue.

Materials and methods
Patient Selection:
A total number of 15 patients suitable for surgical resection and/or
radiofrequency ablation of liver metastases will be included and examined
maximum 24 hours before celiotomy after which the liver is investigated by both
visual and palpatory inspection of the liver and intraoperative ultrasound
(IOUS). Inclusion criteria are a WHO performance status of 0-2 [2], adequate
cardiopulmonary function as well as adequate haematological, renal and hepatic
function. Patients with a known contrast allergy, patients unable to hold their
breath for a sufficient period of time and patients unable to obey breath-hold
commands will be excluded.

Imaging Protocol:
The dynamic CT perfusion measurements will be obtained on a 64-slice
multi-detector CT scanner (Somatom Sensation, Siemens, Erlangen, Germany). A
twelve phase scan is acquired before and 11-times after rapid intravenous
injection (6ml/s) of 100 ml low-osmolar non-ionic contrast agent with an iodine
concentration of 300mg/ml (Ultravist-300 Iopromide; Schering A.G., Berlin,
Germany) and 20ml saline chasing bolus into the left antecubital vein using an
injection pump through an 18g needle. To start the post-contrast scans, bolus
tracking (threshold 100 H.U.) is used placing a region of interest (ROI) in the
right atrium. With a minimal interscan delay of 4 seconds in between two series
the 1st four series were obtained in one single breath-hold at maximum
inspiration. After these first series one breath out and breath in again
command (lasting 8 seconds) was given before adding two series again in one
single breath-hold at maximum inspiration, this was repeated until a total of
twelve series were acquired. The tenth series (considered as the portovenous
phase series) consists of a single breathhold scan in which the entire (upper
and lower) abdomen is scanned at conventional tube voltage and current (120kV
and maximum 180mAs with dose modulation). In all other series a fixed lower
tube current is used to reduce radiation exposure (120kV and 80mAs). All images
are initially reconstructed using thin overlapping axial slices for optimal
visualization in the multiplanar reconstruction mode of the 3D fusion program.

Postprocessing:
Image fusion will be performed with a commercially available 3-D image fusion
program (Leonardo Working Station, Siemens, Erlangen, Germany). The twelve
series are fused by automated (either fully automated or by using reference
points) and/or manual image shifting using both coloured transparent image
overlay methods and image subtraction techniques [Fig. 2]. The tenth and
portovenous phase series will be chosen as reference.

For quantification of liver tissue perfusion and for the creation of blood flow
maps the software program Basama Perfusion 3.0.4.8 (Kanazawa, Ishikawa, Japan)
[5] will be used. This program estimates tissue perfusion as the maximum slope
of the tumour time-density curve divided by the peak arterial enhancement [7,
8].

The mathematical technique has previously been fully described elsewhere [6].
Due to the dual blood supply of the liver, hepatic tissue perfusion is divided
into hepatic artery and portal vein perfusion as the maximum slope of the
tumour time-density curve before versus after the splenic peak enhancement
divided by respectively the peak aortic and portal enhancement.

Potential risks and side-effects
Since the dynamic CTP scan will fully replace the 4-phase CT as pre-operative
evaluation within this study only the additional risks and side-effects due to
the different scanning protocol and contrast administration will be described.
Because the 4-phase CT images can be fully deducted from the 12-phase CT images
within the CTP protocol no disadvantages in the pre-operative evaluation are to
be expected, although the lower mAs in 3 out of 4 phases might somewhat
decrease the image quality. Nevertheless, the most important phase for
morphology of the lesions and therefore the pre-operative evaluation remains
the portovenous phase at which conventional kV and mAs will be used for optimal
image quality.

Adverse effects & other effects of the contrast administration protocol:
Since in the routinely used 4-phase CT scan for the pre-operative evaluation
the same amount and same contrast material is administered, no additional
adverse effects are to be expected in this novel imaging protocol. In the CTP
protocol the rate of contrast administration is somewhat higher (6ml/sec
compared to the conventional rate of 3 - 4ml/sec). In the literature and in our
extended experience with this injection rate no additional side effects have
ever been described or seen. Nevertheless, patients with a history of
cardiopulmonary disease or deteriorated cardiac function will be excluded to
avoid theoretical cardiac decompensation or pulmonary oedema due to the small
but rapid increase of the total circulating volume.

Radiation dose:
Dynamic CT scans will be performed with a tube currrent of 80mAs to reduce
radiation exposure to patients and to improve contrast resolution of iodine
based contrast agents. Again the CTP scans will replace the conventional
4-phase CT scans since all of these four phases can be deducted from the CTP
scan. The effective dose as computed according to the Monte Carlo simulations
for anthropomorphic phantoms (CT-Expo; G. Stamm, Medizinische Hochschule,
Hanover, Germany) and expressed according to the International Commission on
Radiological Protection recommendations [7] is approximately 24,0mSv (11 x
1.5mSv + 1 x 7.5mSv) for the dynamic CTP and 20.7mSv for the routinely used
4-phase CT abdomen (3 x 4.4mSv + 1 x 7.5mSv). Therefore the additional
radiation exposure compared to the conventional 4-phase CT scans in these
patients is +15.9%.

The purpose of this study is to compare routine multiphase (4-phase) CT images
of the liver with ultra-fast total volume multiphase (12-phase) dynamic CTP of
the liver for the detection of small and occult liver metastases and for local
tumour extent, using automated 3D image fusion, taking the intraoperative
inspection and ultrasound, performed maximum 24 hours after the scan, as the
gold standard. A secondary goal will be the correlation with histology (after
surgical resection of liver lesions) in which we hope to determine whether the
rim of high arterial perfusion surrounding liver metastases represents reactive
normal liver parenchyma or true tumour tissue.

nvt

nvt