IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO.
5, MAY 2015
Apparent Ultra-High -Value Diffusion-Weighted
Image Reconstruction via Hidden Conditional
Random Fields
Mohammad Javad Shafiee*, Shahid A. Haider, Alexander Wong, Dorothy Lui, Andrew Cameron,
Ameen Modhafar, Paul Fieguth, and Masoom A. Haider
Abstract—A promising, recently explored, alternative to
ultra-high -value diffusion weighted imaging (UHB-DWI) is ap-
parent ultra-high -value diffusion-weighted image reconstruction
(AUHB-DWR), where a computational model is used to assist in
the reconstruction of apparent DW images at ultra-high -values.
Firstly, we present a novel approach to AUHB-DWR that aims
to improve image quality. We formulate the reconstruction of an
apparent DW image as a hidden conditional random field (HCRF)
in which tissue model diffusion parameters act as hidden states in
this random field. The second contribution of this paper is a new
generation of fully connected conditional random fields, called the
hidden stochastically fully connected conditional random fields
(HSFCRF) that allows for efficient inference with significantly
reduced computational complexity via stochastic clique structures.
The proposed AUHB-DWR algorithms, HCRF and HSFCRF,
are evaluated quantitatively in nine different patient cases using
Fisher's criteria, probability of error, and coefficient of variation
metrics to validate its effectiveness for the purpose of improving
intensity delineation between expert identified suspected can-
cerous and healthy tissue within the prostate gland. The proposed
methods are also examined using a prostate phantom, where the
apparent ultra-high -value DW images reconstructed using the
tested AUHB-DWR methods are compared with real captured
UHB-DWI. The results illustrate that the proposed AUHB-DWR
methods has improved reconstruction quality and improved inten-
sity delineation compared with existing AUHB-DWR approaches.
Index Terms—Apparent diffusion weighted imaging, conditional
random field, diffusion weighted imaging, hidden state, magnetic
resonance imaging (MRI), prostate cancer imaging, stochastically
fully connected random field, ultra high -value.
I. INTRODUCTION
P ROSTATE cancer is the second most common type of
cancer and the sixth leading cause of death due to cancer
among males [1]. In 2013, there were roughly new
Manuscript received August 29, 2014; revised November 08, 2014; accepted
November 18, 2014. Date of publication December 02, 2014; date of current
version April 29, 2015. This work was supported in part by the Natural Sciences
and Engineering Research Council (NSERC), in part by the Canada Research
Chairs program , and in part by the Ontario Ministry of Research and Innovation.
Asterisk indicates corresponding author.
*M. J. Shafiee is with the Vision and Image Processing (VIP) Research
Group, Department of Systems Design Engineering, University of Waterloo,
Waterloo, ON, N2T 3G1 Canada.
S. A. Haider, A. Wong, D. Lui, A. Cameron, and P. Fieguth are with the Vision
and Image Processing (VIP) Research Group, Department of Systems Design
Engineering, University of Waterloo, Waterloo, ON, N2T 3G1 Canada.
A. Modhafar and M. A. Haider are with Department of Medical Imaging,
Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5 Canada.
Color versions of one or more of the figures in this paper are available online
at http://ieeexplore.ieee.org.
Digital Object Identifier 10.1109/TMI.2014.2376781
0278-0062 © 2014 IEEE. Translations and content mining are permitted for academic research only. Personal use is also permitted, but republication/
redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.
1111
cases in the United States [2] and in Canada [3] and an
estimated deaths in the United States [2] and 3900 in
Canada. Early detection of prostate cancer has shown the five
year survival rate to be 98% [2], but prognosis drops to poor
with later detection [4].
A popular detection approach is the prostate-specific antigen
(PSA) test which measures the levels of this antigen in the blood,
where high levels indicate high risk of prostate cancer. Due to
PSA level variability as a result of factors other than prostate
cancer, this approach has led to controversy over its potential for
overdetection and overtreatment [4], [5]. Typically, following
positive PSA screening, the patient is subjected to systematic
transrectal ultrasound (TRUS) guided biopsy where eight or
more samples are collected from the prostate for further anal-
ysis. Localizing the cancer using this approach is invasive and
uncomfortable for the patient. This approach also provides a low
range of visibilty resulting in a high sampling error rate [6].
It is therefore desirable to use minimally invasive diagnostic
and investigative technologies for patient comfort and technolo-
gies that provide large ranges of visibility, such as imaging.
There are various imaging modalities which can be used for
prostate cancer detection. These include TRUS [7], positron
emission tomography (PET) [8], and magnetic resonance
imaging (MRI)[9]; however, all three methods have their
respective drawbacks. TRUS has difficulty in localizing cancer
foci as many tumors in the prostate gland are isoechoic and
cannot be differentiated from surrounding tissue [7]. In PET,
the spatial resolution achieved may not be adequate to properly
localize and detect early stage prostate cancer [8]. MRI (partic-
ularly T2-weighted MRI), although useful for cancer detection
due to improved contrast between soft tissues [10], [11], has
difficulty distinguishing tumors located in the central gland
from low-signal intensity noncancerous formations [12], [13].
One promising imaging modality for detecting cancerous re-
gions in the prostate gland is diffusion-weighted MRI (DWI)
[14]. DWI leverages the differing diffusion behavior of water
molecules in tissues of differing density, allowing the differ-
entiation between healthy and the higher cellularly dense can-
cerous tissues in the prostate gland [15]–[17]. As such, due to
the restriction of water movement from the higher cellular den-
sity, DWI has been employed for increased delineation between
healthy and cancerous tissues [12], [18], [19].
DWI acquisitions are defined by their -values, where the
-value is defined by the amplitude, duration and temporal
spacing of the DWI gradient pulses which allows for the
1112
probing of different diffusion times and length [20]. DWI col-
lected at higher -values (e.g., greater than 1000 s mm ), called
ultra-high -value DWI (UHB-DWI), allows for increased
delineation between tumors and benign tissues [14], [20]–[23]
and is useful for prostate cancer localization.
Compared to lower -values, a high -value is able to sup-
press capillary perfusion effects [24], [25] and reduce high
signal intensity occurrences unrelated to diffusion restriction
such as T2 shine-through [26] that could interfere with image
clarity. Improved delineation is possible as a result of the
different cellular density that causes the recoverable signal to
differ between cancer and noncancerous regions. However, a
challenge faced in UHB-DWI is that the acquired images at
high -values have low signal-to-noise ratio (SNR) [27]–[29].
Current methods for improving SNR performance in DWI are
performing signal averaging over a region of interest [27] or
to perform multiple DWI acquisition1 at a single -value and
average the data [28], leading to the extraction of more reliable
estimates of the DWI signal. Spatial averaging over a region
runs the risk of losing textural features and edge structures and
with UHB-DWI, in particular, long scan times make multiple
acquisitions prohibitive [20], [29].
An alternative approach to achieving UHB-DWI that has
been gaining interest in recent years is the concept of apparent
ultra-high -value diffusion-weighted image reconstruction
(AUHB-DWR) [20], [21], [27]–[29]. AUHB-DWR uses a
computational model to assist in the reconstruction of apparent
DW images at very high -values on the basis of lower -value
DWI acquisitions. The key advantage of AUHB-DWR is that
it allows for the clinical assessment of the prostate at higher
apparent -values than can be achieved using direct acquisitions
limited by significant SNR drop-off. The decrease in SNR by
direct acquisition is a result of imaging hardware limitations
in producing long gradient pulses and magnetic field inhomo-
geneities, long echo times (TE), and motion artefacts, to name
a few [15]. As such, the reconstructions are more useful to ra-
diologists for diagnostic purposes [20]. In addition to improved
image quality, studies have shown that AUHB-DWR may
improve tumor detection [29]–[31] and contrast-to-noise ratio
(CNR) by avoiding the artefacts caused by the long TE asso-
ciated with ultra high -values [20]. It is important to note that
ultra-high -value DW images produced using AUHB-DWR
methods are not equivalent to actual DW images acquired
under similar diffusion time acquisition conditions. For the
sake of correctness, we will refer to the images produced from
AUHB-DWR as apparent ultra-high -value DW images.
This paper presents a novel approach to AUHB-DWR that
aims to improve image quality via the concept of hidden states.
The contributions of this research are divided into two parts:
1) On the basis of conditional random fields, we propose
a new technique for computing AUHB-DWR utilizing
hidden states to model the relationship between tissue dif-
fusion parameters and DWI [hidden conditional random
field (HCRF)] simultaneously. Since this method uses a
model-based approach, the computed AUHB-DWR is less
1The number of measurements (excitations) that are incorporated in aver-
aging during a scan is represented by #-NEX.
IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015
sensitive to noise and has higher contrast between expert
identified tissue as suspected cancer and noncancerous
tissue.
2) A new statistical random field, the hidden stochastically
fully connected conditional random field (HSFCRF) is pro-
posed. The HSFCRF is an extension of fully connected
random fields where the cliques are determined stochasti-
cally. Based on these clique structures, this novel random
field utilizes the merits of fully connected random fields,
but with lower computational complexity.
The rest of the paper is organized as follows. First, a review
of related work is described in Section II, followed by the
methodology where the stochastically fully connected CRFs
are presented in Section III. Hidden states are then introduced
in Section III-C. Finally, the experimental results are presented,
followed by the associated discussion and conclusions in
Sections IV and V.
II. RELATED WORK
The related work is divided to present the related approaches
in literature which concern the two main contributions of the
paper: AUHB-DWR and random fields.
A. AUHB-DWR
Various AUHB-DWR approaches have been proposed in re-
search literature[20], [21], [27]–[29]. These approaches all re-
late -value acquisitions using computational models by esti-
mating tissue diffusion parameters [20], [27]–[29], [32]. For ex-
ample, based on the standard mono-exponential model [32], the
relationship between DW images ( ), at -value and ,
respectively, is assumed to be mono-exponential [shown in (1)],
where is the apparent diffusion coefficient (ADC) value, is
the -value associated with signal intensity , and is the ref-
erence signal intensity associated with
(1)
Mono-exponential models have been shown to not fit empir-
ical decay curves as well as bi-exponential models in -values
ranging from several tens of s mm to 3000 s mm [33], [34].
The bi-exponential model models the two contributing factors
to signal attenuation in DWI, fast diffusion, typically associated
with bulk flow and micro-circulation in capillary networks, and
slow diffusion. The relationship model is shown in
(2)
where and are the apparent amplitudes of the signal
associated with fast and slow diffusion components and
and are the fast and slow ADCs. This approach better
models the diffusion at -values of several tens of s mm which
contribute to the signal attenuation with increasing -value quite
significantly [33], [34]. As such, alternatives to the mono-expo-
nential model [33]–[37] provide a much better explanation of
the DWI signal, and may lead to significant enhancements.
As such, in existing AUHB-DWR approaches such as [21],
[28], [29], the tissue diffusion parameters are first estimated
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS
based on the available DW images and the tissue diffusion
model being employed [e.g., (1) or (2)]. Afterwards, the
apparent DW images at high -values are generated based
on the tissue diffusion model, the estimated tissue diffusion
parameters of that model, and the reference signal . A key
component of AUHB-DWR is the reliable estimation of the
diffusion parameters. The diffusion parameters quantify the
diffusion properties of the tissue, which several works have
sought to estimate using the mono-exponential model [21],
[32]. The two-point (2P) approach [30] is the simplest and most
common approach, where two DWI acquisitions are used to
compute the diffusion parameters using the formulation in (1)
or (2). The key issue with the 2P approach is that it is more
sensitive to the presence of noise in the DWI acquisitions and
only two -values are used to compute the ADC.
A more robust approach for computing the tissue diffusion
parameters is the least-squares (LS) approach of [21]. The goal
here is to determine the diffusion parameters that minimize the
weighted sum-of-squares difference between a set of DWI ac-
quisitions and the set of DWI that are computed using this set of
parameters. The use of the LS approach for AUHB-DWR has
several weaknesses. First, based on the foundation of the LS
approach, it is assumed that the noise of the observations is nor-
mally distributed, whereas noise in DW images obeys a Rician
distribution [38]. A second drawback of this approach is that the
estimated pixels in the AUHB-DWR are assumed independent,
given the set of observations, while pixels real DWI are in fact
are related to surrounding pixels [27], [28].
To address the first issue of the LS algorithm, Walker-Samuel
et al. [32] proposed a new algorithm to compute the diffusion
parameters based on maximum likelihood (ML) estimation.
They incorporated the Rician distribution formulation in the
ML algorithm to better account for noise and then they esti-
mated the parameters. However, their method computed each
pixel of the DW image independently and did not incorporate
the relationships between neighboring pixels in the image. In
contrast, our proposed new HCRF and HSFCRF approaches
incorporate short distance and long distance relations of states,
respectively, and as a result can preserve edge structures in
addition to incorporating neighboring relationships.
B. Random Fields
Conditional random fields (CRFs) proposed by Lafferty et
al. [39] are a new generation of random fields which use a
probabilistic framework for classifying data. By using CRFs,
the direct modelling of conditional probability of states given
measurements becomes tractable. Before CRFs, the conditional
probability of states given measurements was approximated
based on a prior and likelihood models, such as the hidden
Markov model [40]. This approximation has the drawback of
assuming the conditional independence of measurements given
states [41]. Since CRFs model the conditional probability of
states given measurements directly, the conditional indepen-
dence assumption is relaxed and, as a result, the model is more
accurate.
After Lafferty et al.'s seminal work, researchers applied the
CRFs in various applications [42]–[44] including image model-
1113
ling and medical imaging. Arton et al. [45] proposed cost-sen-
sitive CRFs to segment tumor regions in the prostate gland, for-
mulating a binary segmentation problem for the CRFs to deter-
mine cancerous regions from others. Similarly for brain tumor
segmentation, the authors of [46] used a CRF with binary seg-
mentation. The motivation of obtaining CRF models in medical
applications is due to the high spatial correlations of anatom-
ical objects. In other words, it can be assumed that neighboring
pixels should have the same characteristic in the image.
The basic structure of an image is a grid in which each pixel
is connected to four neighbors. This can be represented by
the basic CRF, called an adjacency (local) CRF, which been
shown to be effective in image modelling [47], [48], however,
the very short-range neighborhoods introduce a weakness.
Since the basic CRF utilizes unary and pairwise potentials on
local neighborhoods, these adjacency CRFs lead to smoothed
image boundaries as they are not able to incorporate long-range
relations among nodes. In order to improve the accuracy of la-
belling problems, the basic CRF framework has been expanded
to incorporate hierarchical connectivity [49], [50].
Assuming a Gibbs distribution [51], the probability of a set
of states given the observations can be formulated as an expo-
nential of the energy function over cliques. To maximize the
conditional probability, the nodes' states change until the energy
of the random field reaches an equilibrium. For local random
fields characterized by a first-order Markov model, the energy
penalizes the dissimilarity of neighboring nodes, thus equilib-
rium is achieved when proximate nodes have nearly the same
state value, leading to a degree of smoothness on any bound-
aries. However given a model which includes long-range con-
nections, it is possible to broaden the definition of energy to in-
clude spatial relations beyond those of contrast between neigh-
boring states, allowing richer spatial information to be incorpo-
rated in the modelling, which in general leads to a better preser-
vation of boundaries.
Fully connected CRF frameworks were proposed on semantic
image labeling [52], however the complexity of inference in
fully connected CRF models limited their usage to sets of hun-
dreds of image regions. Techniques have been developed to ad-
dress this issue [53]–[55] by concentrating on the computational
complexity of training and the inference steps in fully connected
random fields. Krähenbühl and Koltun [55] provided Gaussian
kernels as feature functions and formulated CRF inference as a
filtering problem. The feature functions are convolved to each
node, like a filtering procedure, to calculate the energy func-
tion in each minimization step. Thanks to the permutohedral
lattice [56], the computational complexity of the convolution
[i.e., ] is reduced to linear [i.e., ]. Following this
approach, Zhang et al. [53] utilized the stationary assumption
to relax the Gaussian assumption proposed by Krähenbühl and
Koltun [55]. They believed that the spatial potentials over two
pixels depend only on their relative positions for each category.
Therefore, more statistics could be encoded by using different
distributions. For example, the geometry distribution can be de-
fined based on the relative position of an object such that “cow”
and “grass” should be close together. Campbell et al. [54] gen-
eralized the pairwise potentials to nonlinear dissimilarity mea-
sures. They presented the pairwise terms as density estimates of
1114
the conditional probabilities which were expressed by dissimi-
larity measures between nodes. Finally, an efficient approxima-
tion technique was used to find the set of feature spaces and
thereby encoding the dissimilarity measures as Euclidean dis-
tances.
The above mentioned approaches tried to reduce the compu-
tational complexity of the inference procedure by changing the
potential functions and using a convolution approach. Although
they can decrease the computational complexity of the problem,
the feature functions are limited to some specific types of fea-
ture functions.
Here, we define the AUHB-DWR in the context of CRFs. To
the best of our knowledge, this is the first time that reconstruc-
tion of apparent high -value DW images is computed using
this framework. We address the AUHB-DWR by two different
approaches. The first approach uses a local CRF to model the
adjacency relations among close signal intensities. We formu-
lated the AUHB-DWR by a hidden conditional random field
which computes the tissue diffusion parameters in the hidden
states. Second, we propose a new configuration to relax the
computational complexity of a fully connected CRF. Stochastic
cliques are a novel type of clique sampling where the configura-
tion of the fully-connected graph is sampled with relatively few
connections. We will formulate the AUHB-DWR by a hidden
stochastically fully connected conditional random field which
computes the tissue diffusion parameters in the hidden states as
well. It is important to emphasize that the effect of noise present
in the DWI acquisitions is compensated for in the proposed ap-
proaches by incorporating the noise model and the spatial re-
lationships among different pixels, and more details regarding
this are provided in Section III-C.
III. METHODOLOGY
The problem that we wish to tackle in this work is to per-
form AUHB-DWR, given a set of DW images acquired at lower
-values, in a reliable and robust manner. Based on the tissue
diffusion model (e.g., mono-exponential or bi-exponential, as
presented in (1) and (2), respectively), we model the conditional
probability of an AUHB-DW image given a set of lower -value
DWI acquisitions. In this section, two different frameworks are
proposed: HCRF and HSFCRF.
The common CRF (local CRF) is utilized to model the
relations among signal intensities in various DW images and
the tissue diffusion parameters. Our novel method exploits the
advantages of fully connected random fields, but at reduced
computational complexity, preserving the image discontinuities
and boundaries. This allows for improved AUHB-DWR image
quality by taking into account the spatial and noise characteris-
tics of the underlying data while improving contrast between
cancerous and healthy tissues. The following section explains
the proposed methods in detail.
A. Conditional Random Fields
The conditional random fields (CRFs) approach models the
conditional probability of the state set given the measurement
, , by a general exponential formulation
(3)
IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015
Fig. 1. Realization of a HCRF graph. As shown, the HCRF is a combination
of three graphs: a state graph, a hidden state graph, and a measurements graph.
For better visualization, the hidden states are shown inside the final states and
the measurements are unified as one square. Actual realization of each element
of the random field is demonstrated to the right: is the state, the hidden state
and the measurement. Each node is connected to its four
closest neighbors.
where is the partition function and is some combi-
nation of unary ( ) and pairwise ( ) potential functions
(4)
Here is a single state in the set , is the
clique structure, is the subset of states (clique), and
is the set of observations. is the number
of random variables in the CRF that is specified by the number
of pixels present, since each pixel is considered as a random
variable. Each node is connected to its four nearest nodes in
local CRFs. Incorporating longer connection ranges in a direct,
deterministic manner imposes more computational burdens that
are not tractable.
The potential functions and from (4) are the com-
binations of unary and pairwise feature functions and their cor-
responding weights , respectively
(5)
(6)
where the constants control the importance of each feature
function in the energy formulation calculated in the training
stage.
We then utilize a local CRF to model the interactions among
signal intensities. A hidden state corresponding to each random
variable is defined to estimate the tissue diffusion parameters
based on available DW images parallel to the reconstruction of
apparent high -value images. Fig. 1 demonstrates a realization
of the hidden CRF used in modeling. Next, we propose a novel
type of random field, by taking advantage of fully connected
random fields which have less computational complexity.
B. Stochastically Fully Connected CRF
Stochastically fully connected conditional random fields
(SFCRFs) [57] are fully connected random fields constructed
based on stochastic cliques. All nodes can be connected to
other nodes (fully connected), however, the cliques for each
node are determined based on distribution probabilities, so the
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS
Fig. 2. Realization of a HSFCRF graph. As shown, the HSFCRF is a combina-
tion of three graphs like as CRF in Fig. 1. Connectivity of each pair of nodes
and is determined by the edge . Closer nodes are connected with a higher
probability (black solid edges), whereas two nodes with a greater separation are
less probable to be connected (red dashed edges).
number of pairwise cliques in the graph may not be the same as
the number of neighborhood pairs.
Each node has a set of neighbors
(7)
where . The specified clique structure , in this
paper, taken to be the pairwise clique
(8)
(9)
for node is determined based upon a stochastic clique
indicator function, , to distinguish whether two nodes
can construct a clique according to a pre-defined distribution.
For image modeling, this function must consider the spatial re-
lation among the nodes and must involve data driven into the
model. Therefore, the proposed indicator function is the combi-
nation of spatially driven and data driven probabilities
(10)
otherwise
applies two types of information on determining the
node connections: spatial information ( ) and the data rela-
tion among the states ( ). The threshold determines the
sparsity of the graph. The spatial information and data in-
formation can be selected arbitrarily based on the problem.
Here we assign two Gaussian distributions based on the Eu-
clidean distance between two nodes to compute while the
signal similarity is utilized to define . to tackle.
Fig. 2 illustrates an example of a SFCRF. Any two nodes in
the graph can be connected, however, to improve visualization,
only the connectivities of the center node are shown. The prob-
ability of connecting two nodes as a clique is different for each
pair of nodes and has an inverse relation by the distance be-
tween them. According to this probability, there is a possibility
for two distantly separated nodes and to be connected, as
illustrated in Fig. 2, enabling the SFCRF to take advantage of
the fully connected CRF.
By sampling the configuration of a fully connected random
field, the proposed SFCRF provides the merits of fully con-
nected random fields. However, the connectivity of pairwise
nodes is based on the stochastic clique indicator, therefore,
1115
many pairwise nodes will likely be disconnected and as a result,
the SFCRF has reduced computational complexity over fully
connected random fields.
C. Hidden State
An interesting challenge associated with the problem of
AUHB-DWR is the fact that the tissue diffusion parameters
must also be estimated alongside the AUHB-DWR. As men-
tioned earlier, a popular strategy taken to address this issue is
to first estimate the parameters according to the set of lower
-value DWI acquisitions. Then, given the set of low -value
DWI acquisitions, the estimated parameters, and the tissue
diffusion model [as expressed in (1) or (2)], along with the in-
dependence assumption amongst pixels, the new AUHB-DWR
estimation problem becomes
(11)
where is the tissue diffusion model, is the set of estimated
model diffusion parameters, is a DW image corresponding
to , and is a new AUHB-DWR image corresponding to .
There are two main drawbacks to adopting such a strategy
to deal with tissue model diffusion parameters in the context of
AUHB-DWR.
1) Spatial relationships are not taken into account in the es-
timation and each pixel is estimated independently. How-
ever, pixels within a AUHB-DWR image have spatial re-
lationships amongst themselves. Incorporating these rela-
tionships would lead to superior modelling and estimation
of the AUHB-DW image.
2) The estimation procedure for AUHB-DWR is sub-divided
into two estimation stages that are solved separately:
i) tissue model diffusion parameter estimation and ii)
AUHB-DW image estimation. Dividing the problem
into two stages imposes a greater estimation error on the
solution. As such, given that the two stages are solved
separately, the estimation error propagates and the solution
obtained using this approach is sub-optimal for both the
tissue diffusion parameters and AUHB-DWR as a whole.
The first drawback can be addressed through the use of Markov
random fields (MRFs) [58], [59]. However, since MRFs involve
the relationships within neighborhoods, the resulting adjacency
structure is limited in its ability to model long range connec-
tions and generally results in excessive smoothing of object
boundaries. The second drawback requires a different strategy
Here, we present a novel method to address all of the above is-
sues simultaneously. Since the goal is to estimate a AUHB-DW
image ( ), the estimation of the tissue model diffusion param-
eters ( ) can be considered as a hidden state in the modelling
procedure. As such, we can formulate the problem as HCRF or
a hidden SFCRF (HSFCRF) in which the model diffusion pa-
rameters are the hidden state
(12)
where is the AUHB-DW image, is the set of
lower -value DWI acquisitions and is the hidden state rep-
resenting the tissue model diffusion parameters. As seen in the
1116
right hand side of Figs. 1 and 2, each node in the HCRF or HS-
FCRF is a combination of the actual state (the UHB-DW image),
the hidden state (the model diffusion parameters corresponding
to a single state), and the measurements (the given set of lower
-value DWI acquisitions). As such, we arrive at the following
energy function for HSFCRF or HCRF we wish to minimize:
(13)
where is the combination of unary and
pairwise potential functions. The potential functions
determine the relations among the tissue model parameters, the
given DWI acquisitions, and the new AUHB-DW image. By
involving the tissue model diffusion parameters as a hidden
state in the SFCRF or CRF formulation, the new AUHB-DW
image and the diffusion parameters will be estimated simulta-
neously; hence the propagation error is attenuated.
The unary feature functions are defined by the tissue diffusion
model, DWI acquisitions, and AUHB-DW images
(14)
(15)
where is the node or pixel of the DWI acquisition,
is a constant value and is fixed to 0.5 and is the Rician
noise variance. Since the DW images obey the Rician distribu-
tion, an asymptotic variance stabilization transform (VST) [38]
is taken into account, to incorporate the VST in the unary fea-
ture function. All feature functions are evaluated for all DWI
acquisitions; the pairwise potential function can be formulated
as
(16)
where and are unary and pairwise weights of feature func-
tions corresponding to each of the DWI acquisitions, is the
feature function applied on DW image and specifies
the number of pairwise feature functions.
Thanks to the fully connected merit of the HSFCRF, this pro-
posed model provides long-range relationships among nodes in
the random fields and, therefore, preserves the discontinuities
and boundaries. The main difference between HCRF and HS-
FCRF is the definition of cliques in the random field. HSFCRF
is the general framework of CRF that is changed to a HCRF if
the underlying stochastic clique distribution is changed to four
neighboring pixels.
D. Training and Inference
Maximum likelihood is a common method used to estimate
the parameters of random fields. The training step is completed
by maximizing the log-likelihood on the training data, where the
IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015
training parameters' objective function can be formalized as
(17)
where is a regularization term that controls the value of
which is estimated by cross validation. As the log-likelihood
function is concave, the parameters can be chosen such that
the global maximum is obtained and the gradient or vector of
partial derivatives with respect to each parameter becomes zero
(18)
(19)
where are all configurations of states.
Since the problem we wish to solve here is the estimation of
AUHB-DW images based on a set of lower -value DWI ac-
quisitions, the DWI acquisitions are typically treated as having
equal contributions to the estimation of the diffusion parameters
and AUHB-DW images. In clinical practice, one can bypass the
training phase based on this prior information and select
for all unary feature functions.
The for each pairwise term was calculated based on a set of
neighbors of each node using a contrast sensitive approach [60]
of the observation
(20)
where is the window centered by node with a specified size
and is the window centered by node , (the neighbor of node
on DWI image ). Here, the Euclidean similarity is selected as
the only pairwise feature function, therefore, . The degree
of smoothness and effect of each region are controlled by .
is dependent on the problem and the spatial relation among
random variables. The value of is chosen by an expert based
on cross validation and is assigned manually. However, it can
be trained if enough annotated data is available. The solution
was inferred by gradient descent approaches. Since the states
are considered as continuous, the belief propagation approach
is simplified by a gradient descent procedure.
IV. RESULTS AND DISCUSSION
A. Experimental Setup
The effectiveness of the proposed methods for AUHB-DWR
was evaluated on an MRI training phantom and nine patient
cases with prostate cancer.
1) Phantom Experiments: It it worthwhile to note that the
main purpose of phantom study is to examine the robustness of
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS
the proposed methods against noise, since the microstructure of
phantom case is not similar to the biological tissues.
A set of phantom experiments were conducted to examine
the robustness of the proposed reconstruction methods to
the presence of noise. The MRI training phantom used was
a multi-modality prostate training phantom from Computer-
ized Imaging Reference Systems Inc (CIRCS Model 053).
The phantom is composed of a clear acrylic container with
dimensions 11.5 cm 7.0 cm 9.5 cm with a front probe
opening of 3.2 cm diameter and a rear probe opening of 2.6
cm diameter. The prostate is composed of high-scattering Blue
Zerdine with dimensions 5 cm 4.5 cm 4.0 cm and is placed
in a background gel similar to water with little backscatter
attenuation ( ). Within the prostate, there
are three randomly placed lesions of sizes between 0.5–1.0
cm, hypoechoic to the prostate. The urethra and rectal wall are
made of low scattering Zerdine with diameter of 0.7 cm and
dimensions 6 cm 1 cm 0.5 cm, respectively. This phantom
was imaged with an inflatable Medrad eCoil ERC using DWI.
Note that while the microstructure of the phantom used does
not mimic the diffusion dynamics of biological tissues, it does
provide a good testbed for evaluating noise resiliency of the
reconstruction methods.
The DWI MRI was acquired by a 3T GE Discovery MR750.
DWI was collected at s mm at
3-NEX2 and s mm 8-NEX and used to reconstruct
s mm collected at 16-NEX. For the DWI data, the
echo time (TE) was 71.70 ms and repetition time (TR) was
ms.
2) Patient Experiments: The effectiveness of the proposed
method was also evaluated on nine patient cases with prostate
cancer. The patients ranged in age is from 58–80 years, with
a median age of 69. Institutional research ethics board approval
and patient informed consent for this study was obtained at Sun-
nybrook Health Sciences Centre in Toronto, Canada.
Patients were scanned using a Philips Achieva 3.0T. The axial
single-shot echo-planar DWI sequences used from the cases
were performed with the following imaging parameters: TR
ranged from 3336–6178 ms with a median of 4890 ms, and
TE ranged from 61–67 ms with a median of 61 ms. The res-
olution of the signal acquisitions ranged from 1.36 mm 1.36
mm to 1.67 mm 1.67 mm, with a median of 1.56 mm 1.56
mm. Slice thickness ranged from 3.0–4.0 mm with a median of
3.5 mm. The display field of view (DFOV) ranged from 20 cm
20 cm to 24 cm 24 cm with a median of 24 cm 24 cm.
The number of -values in each case is either 3, 4, or 6 with the
highest -value being s mm .
B. Diffusion Model
For the experiments conducted, the diffusion model chosen
was the mono-exponential model. The rationale for choosing
this model over the more descriptive bi-exponential model,
leads from the discussion brought up by Koh et al. [28] about
how many -value acquisitions are required and they exist to
warrant using the model. Due to the doubling of parameters
from the mono to bi-exponential models, more -values are
2Number of Excitations
1117
needed to estimate the true signal attenuation. In the retro-
spective studies that we have provided, which are acquired
using typical clinical patient protocol for prostate imaging,
only a limited number of -values are acquired for a number
of reasons (e.g., reducing patient discomfort, reducing motion
artifacts, hospital and doctor recommended procedure etc.)
and as such are insufficient to determine the tissue diffu-
sion parameters of the bi-exponential model. Therefore, we
will use a mono-exponential model 1 when calculating the
tissue diffusion parameters (i.e., the ADC) for the experi-
ments conducted. However, alternatives to the mono-expo-
nential model [33]–[37] provide a much better explanation of
the DWI signal, and may lead to significant enhancements in
the proposed method and is thus important to explore in the
future.
C. Competing Algorithms
The proposed algorithm was compared against both base-line
and state-of-the-art algorithms for AUHB-DWR.
• 2P [30] 2-point estimation based on the exponential rela-
tionship in (1). The ADC value was calculated with DWI
acquisitions at s mm and s mm , and the
AUHB-DW image is calculated using the estimated ADC
value and the DWI acquisition at s mm as the ref-
erence signal.
• LS [21], [32] The ADC value is calculated based on a least
squares formulation and the AUHB-DW image is calcu-
lated using the estimated ADC value and the DWI acqui-
sition at s mm as the reference signal.
• ML [32] This estimation algorithm incorporates the Rician
distribution in a maximum likelihood formulation and es-
timates the ADC value. As with the 2P and LS approaches,
the AUHB-DW image is calculated using the estimated
ADC value and the DWI acquisition at s mm as
the reference signal.
The LS and ML parameters were chosen based on [32]. The
proposed algorithms will be referred to as HCRF and HSFCRF
in the following sections, figures and tables.
D. Quantitative Analysis
In addition to coefficient of variation of signal intensity (CVI)
(22) [61] and coefficient of variation of contrast (CVC) (23), the
following additional quantitative analysis metrics were used to
evaluate the proposed method. It is worthwhile to mention here
that all the regions referred to in this paper as suspected tumor
regions were identified by an expert radiologist with more than
15 years of experience.
1) Naive Bayes Probability of Error [62] (NBPE): To provide
a quantitative analysis of the results produced by the
tested approaches, NBPE was computed for two selected
regions: i) healthy prostate tissue, and ii) suspected tumor
tissue. Gaussian distribution models are trained on the
pixel intensities of the healthy prostate and tumor regions
to evaluate the separability between the two regions in
the AUHB-DW images. After learning the parameters of
the distributions, the decision boundary between the two
distributions is determined and the expectation of error is
1118 IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015

Fig. 3. NBPE measure is calculated based on overlap of the two estimated

Gaussian distributions for the healthy prostate region and the tumor region. It is
worth to mention that tumor tissues were identified by trained radiologist.

calculated as NBPE. Fig. 3 illustrates the NBPE measure

in an intuitive fashion where the red and blue regions
indicate the expected error.
2) Fisher Criterion (FC) Value: The FC value shows the
smoothness on different regions in terms of the separa-
bility of two types of regions on the estimated AUHB-DW
image. The FC value has direct correlation by separability
of two regions and inverse correlation by the sum of their
variances
(21)
Fig. 4. CIRCS Model 053 Prostate MRI phantom is shown with the selected
tumor region (shown in blue) and prostate region (shown in red). Due to the
spatially variant image intensity and contrast in the image, the region used to
calculate the CVI value is shown by green rectangle.
TABLE I
QUANTITATIVE RESULTS FOR THE PHANTOM CASE: PROPOSED ALGORITHM IS
COMPARED WITH ML, LS AND 2P AND THE TARGET UHB-DWI ACQUISITION,
BY DIFFERENT MEASURES: FC, NBPE, CVC, AND CVI

and are mean intensity values of suspected tumor

and prostate gland regions respectively and and
define these regions' respective standard deviations.
The following sections explain the results of the phantom and
the patient experiments used to evaluate the effectiveness of the
proposed method .
E. Phantom Experiment Results
The accuracy of the proposed algorithm was evaluated using
a prostate phantom. The AUHB-DWR method uses the DWI
acquisitions at s mm to compute
the s mm image. The DW images corresponding to
s mm were acquired using 3-NEX and
s mm was captured using 8-NEX. The apparent
DW images reconstructed by different methods were compared
relative to the actual DW image acquired by the MRI scanner at
16-NEX for reference.
Using prior knowledge of the classifications for the regions in
the phantom, the CVI (22) [61] and CVC (23) of the suspected
tumor and nontumor regions were calculated in addition to the
FC and NBPE for comparison of the tested methods. The re-
gions used in the comparison are shown in Fig. 4. The CVI is
computed as
(22)
where is the mean value of a region and is the standard
deviation of a region. The CVC is computed as
(23)
where is the mean value of the nontumor prostate region,
is the mean value of the suspected tumor region, and is the
standard deviation of the nontumor prostate region. A square
block (green) on the upper left corner of the image (Fig. 4) is
used to calculate the standard deviation and the CVI value for
fair comparison across the methods. This region was selected
due to its homogeneity and as such any signal variation can be
attributed to estimation error.
The quantitative results of HCRF/HSFCRF and other tested
methods were compared with those of the real DWI acquired
at s mm at 16-NEX. Table I summarizes the com-
parison results. As seen in the table, the proposed algorithm
outperforms the real DWI s mm image and other
methods in the FC, NBPE, and CVI metrics. Although the LS
result has the better CVC, this difference is not significant.
It is worth to mention that the HSFCRF preserves the trade
off between CVC and CVI, therefore, the produced result is
very smooth while preserving the contrast difference between
the suspected tumor region and prostate gland. Fig. 5 demon-
strates the visual results for the AUHB-DW images produced
by the tested methods at s mm and the UHB-DWI
acquisition at s mm . Visual results support the
quantitative results demonstrating HSFCRF's improved con-
trast over the other approaches for better classification of sus-
pected tissue regions. The HSFCRF preserves edge bound-
aries better than HCRF and the result is smoother than HCRF
in similar regions.
The effect of the number of pairwise cliques on CVI and
CVC on HSFCRF was also examined on the phantom case.
Fig. 6 demonstrates the evaluated CVI and CVC based on the
expected number of the pairwise cliques used for HSFCRF. It
can be observed that, in general, both CVI and CVC decrease
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS 1119

Fig. 5. AUHB-DW image results generated by different techniques for the phantom case, as compared with the target UHB-DWI acquisition. HSFCRF result
provides better contrast than the other tested methods as well as the target UHB-DWI acquisition. ROI corresponding to this study is demonstrated in Fig. 4. (a)
2P. (b) LS. (c) ML. (d) HCRF. (e) HSFCRF. (f) UHB-DWI.

Fig. 6. CVI and CVC based on the expected number of the pairwise cliques, which is controlled by in (10). In general, both CVI and CVC decreases as the
expected number of pairwise cliques increases. However, the CVI and CVC improvements decrease after the expected number of pairwise cliques exceeds 1500,
with CVI particularly increasing after 1512. Based on this analysis, the expected number of the pairwise cliques used for HSFCRF in the experiments is set to 1512.

as the expected number of pairwise cliques increases; although
increasing the number of pairwise cliques also increases com-
putational complexity. However, it is important to observe that
the CVI and CVC improvements decreases after the expected
number of pairwise cliques exceeds 1500, with CVI particu-
larly increasing after 1512. Based on this analysis, the expected
number of the pairwise cliques used for HSFCRF in the exper-
iments is set to 1512, which is approximately 2% of possible
pairwise cliques in the fully-connected graph. It is worth men-
tioning that inferencing from a fully connected random field di-
rectly with all possible pairwise cliques is not computationally
tractable when the number of nodes is large, such as for the pur-
pose of AUHB-DWR, and thus no such comparisons are made
in this study.
1120 IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015

Fig. 7. AUHB-DW images at an apparent -value of 4000 s mm estimated by the different tested methods for patient case #5. Red arrow identifies the suspected
cancerous region. HSFCRF's estimation results in AUHB-DW images with fewer artifacts, and the suspected tumor is more visually distinguishable from the
surrounding prostate tissue.

TABLE II TABLE III

FC VALUES FOR THE PATIENT EXPERIMENTS: FC VALUES ARE NBPE FOR PATIENT EXPERIMENTS: TO DETERMINE THE SEPARABILITY
CALCULATED FOR THE APPARENT DW IMAGES RECONSTRUCTED BY OF TWO REGIONS IN TERMS OF INTENSITY, NBPE IS EVALUATED FOR
DIFFERENT METHODS (LARGEST VALUES ARE SHOWN AS BOLDED, VARIOUS TECHNIQUES (BOLDED VALUES INDICATE THE LOWEST ERROR).
INDICATING HIGHER SEPARABILITY) RESULTS ARE REPORTED FOR THE PATIENT EXPERIMENT

The value of in (20) is set to 0.2 for computing the ADC

value as it was found empirically to provide strong performance.

F. Patient Experiment Results

The proposed algorithm was examined on nine patient
cases suffering from prostate cancer. Each of these cases
have cancerous regions with a different shape and size. The
goal is to compute the AUHB-DW image corresponding Fig. 8. Evaluated CVC corresponding to various reconstructed apparent
to an apparent -value of 4000 s mm . As explained in high -value DWIs (1500–4000) s mm . Higher -value apparent DWI
Section IV-A, the number of available -values for each DWI has smaller CVC and allows for higher contrast between suspected tumor
regions and the noncancerous prostate regions. Results are reported based
acquisitions were 3, 4, or 6 with the highest -value being on the averaged value of nine patient cases.
s mm .
FC and NBPE results are presented in Tables II and III.
The proposed HSFCRF and HCRF approaches achieved the very sharp and the visual delineation between cancerous re-
highest FC values for all tested patient cases. The results are gions and prostate glands is much better than other methods.
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS 1121

Fig. 9. AUHB-DW images at an apparent -value of 4000 s mm estimated by the different tested methods for patient case #7. Suspected tumor region
is highlighted by the red arrow. Suspected tumor region in the results produced by HSFCRF is brighter, well-contrasted and the boundaries are very clear
when compared with other tested methods.

Experimental results illustrate that incorporating the hidden TABLE IV

state in modeling and reconstruction of the ADC value par-
allel to the DW image has an impact in the accuracy as ex-
pected.
Table V shows the CVC values of the proposed methods
compared to other methods. The results illustrate that the
proposed methods may have improved diagnostic quality in
ultra high computed -value reconstruction compared to other
methods. To illustrate that increasing the -value provides
more contrast between the suspected tumor regions and be-
nign tissues, apparent DW images corresponding to different
high -values from s mm to s mm
are reconstructed using HSFCRF and the CVC calculated.
STUDENT -TEST ANALYSIS; THE RESULTS OF 2-POINT ESTIMATION
ARE USED AS BASED SIGNAL. -TEST ANALYSIS IS PROVIDED
BASED ON THE PATIENT EXPERIMENTS
TABLE V
COEFFICIENT OF VARIATION OF CONTRAST: COMPUTED CVC VALUES
FOR DIFFERENT METHODS TO DEMONSTRATE IMPROVEMENT OF
INTENSITY DIFFERENTIATION OF APPARENT HIGH COMPUTED -VALUE
DWI RECONSTRUCTION BY THE PROPOSED METHODS COMPARED
TO THE OTHER METHODS

Fig. 8 is the average value of CVC for nine patient cases.

As seen higher -value apparent DW images provide smaller
CVC, which implies larger intensity contrast between the sus-
pected tumor region and healthy prostate regions.
Student -tests were also done based on the results of
2-point estimation. Table IV shows the p-values for all
methods. The p-values demonstrate that the performance of
the proposed CRF-based methods were statistically significant
( ).
1122 IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 34, NO. 5, MAY 2015

Fig. 10. AUHB-DW images at an apparent -value of 4000 s mm estimated by the different tested methods for patient case #8. The suspected tumor region is
highlighted by red arrow. Suspected tumor region is clearer in the HSFCRF image than those produced by the other techniques. Moreover, the suspected cancerous
region is brighter in the HSFCRF's result and more distinguishable from the prostate region with a clearer boundary.

Figs. 7, 9, and 10 illustrate the results of the proposed method
alongside 2P, LS, and ML estimation methods for cases #5, #7,
and #8, respectively. As seen in these figures, the AUHB-DW
images produced by the HSFCRF have fewer artifacts than
those produced by the other algorithms, and the contrast be-
tween healthy prostate tissue and suspected cancerous tissue in
the AUHB-DW images produced by the HSFCRF is noticeably
improved, which is very important for the purpose of cancer
screening and diagnosis by radiologists. The compared estima-
tions lack contextual detail in the background which further
hinders the visibility of the cancerous region.
V. CONCLUSION AND FUTURE WORK
In this paper, we proposed a novel approach for generating
AUHB-DW images using the concept of HCRF. To reduce
the propagation error of estimation, we imported the tissue
model diffusion parameter estimation as a hidden state to the
model. Based on this formulation, the computation of the
diffusion parameters and AUHB-CDWR are done simultane-
ously and it reduces the error of calculation. Two different
hidden conditional random field models were introduced,
HCRFs based on short-range interactions, and hidden HS-
FCRF based on both short-range and long-range interactions.
Experimental results from both patient cases and phantom
tests illustrate that the proposed methods outperform the other
state-of-the-art techniques in AUHB-CDWR with higher
separability between tissue, lower probability of error, lower
coefficients of variation of spatial intensity and coefficients
of variation of contrast. Future work involves investigating
different training strategies (currently feature functions are
determined based on standard clinical practice) and study
the behavior of the weighting of each feature function. Fur-
thermore, we aim to apply new state-of-the-art inference
methods to increase the efficiency of the proposed method
and also we aim to validate these results by executing a full
clinical multi-reader study with a larger dataset coupled with
histological ground truth. Furthermore, we aim to investi-
gate more advanced diffusion models [33]–[37] in a more
comprehensive study to evaluate their efficacy for improving
reconstruction quality when used within the proposed ap-
proach. Finally, we aim to investigate the effectiveness of the
proposed frameworks for other medical imaging reconstruc-
tion applications [63], [64].
SHAFIEE et al.: APPARENT ULTRA-HIGH -VALUE DIFFUSION-WEIGHTED IMAGE RECONSTRUCTION VIA HIDDEN CONDITIONAL RANDOM FIELDS
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