MRI Multimodal analysis for early diagnosis / prognosis of

Parkinson’s disease

(IPAL, Geneva Univ. Hospital, Timisoara Univ. Romania, Univ. of Besançon, SGH)

Abstract: We study a Parkinson's disease (PD) prediction system using a specialized diffusion-based approach. A total of
150 subjects, among who 75 patients diagnosed clinically with PD and 75 control cases, underwent DTI imaging (TR/TE
4300/90; 12 directions; 4 averages; 4/0 mm sections; 1.2 x 1.2 mm in-plane resolution). According to our knowledge, this
represents the biggest cohort of PD patients implicated in such a study. T2 images are mainly used by the neurologists for
their anatomical detail. The EPIs have lower resolution but provide essential anisotropy information for the fiber tracking
process. The two volumes of interest (VOI) are represented by the Substantia Nigra and the Putamen. We use the VOIs for
the iconic based registration. For the fusion, we enhance the anatomical part from T2 image and consider the anisotropy
from EPI. After 3D fibers growing, we compute the fiber density (FD), fiber volume (FV) and the fractional anisotropy
(FA). Using content-based image retrieval, we compare patients based on the extracted fibers and evaluate them according
to Hohen&Yahr (H&Y) scale. Our results show that the T-Test on H&Y correlated with FD on the left side has p=0.019
and on the right side p=0.015. Our approach is important from the clinical point of view, providing a new tool for the
neurologists to evaluate and predict PD evolution. From the technical point of view the fusion approach takes the tensor
based information (EPI) and the anatomical detail (T2) from different types of images.

Description of purpose: Parkinson’s disease affects population that has, on average, 61 years, even if it begins around
40 years6. From this point of view, the continuous aging of the population, combined with the actual late detection
(impossibility to reverse or stabilize the PD evolution) justifies concerns for a prediction system. By the time the disease is
detected, the patient has already lost 80-90% of the dopamine cells, those that represent one of the main neurotransmitters1.
The treatments are less effective after the disease develops. Thus a prognosis of this disease could diminish the effect of the
PD or even reverse it.

Method(s): Seventy-five patients diagnosed clinically with PD and seventy-five control cases underwent DTI imaging
(TR/TE 4300/90; 12 directions; 4 averages; 4/0 mm sections; 1.2 x 1.2 mm in-plane resolution) after giving informed
consent. This represents, as far as we know, the biggest cohort of PD patients implicated in a study. The heterogeneity of the
patients – Asians, Eurasians and Europeans - can also be used to characterize a general trend for PD prognosis.

Our method is based on the importance of each DTI image: T2 images are especially used by the neurologists for
their anatomical detail in volumetric analysis. The EPIs are low resolution images, hence the level of detail is poor, but they
provide tensor information for the fiber tracking process. Putting together the anatomical detail provided by the T2 images
with the tensor information taken from EPI images, we obtain a space where we can grow fibers in well defined volumes of
interest.

From our preliminary studies we have seen that the motor fibers are relevant for the progression of PD. By building
a specific CAD for PD, we segment, visualize and quantify VOIs and motor fiber tracts. These VOIs are than compared
with the normal and affected ones using content-based image retrieval (CBIR) approach. Substantia Nigra and Putamen
represent the two VOIs where the motor fibers are placed and from where we extract the bundle of interest. These VOIs are
the landmarks for an iconic based registration11, used to align the volumes for T2 and EPI (Fig. 1). We have chosen this
registration as we are dealing with intra-patient matching. The registration provides a common space for the tensors and the
anatomical elements. The registered volumes are fused, by acquiring the anatomical part from the T2 image and
considering, from the EPI, the anisotropy information containing the tensors and their direction. The fusion enhances the
anatomical importance from the high resolution image (T2) taking into account the same area from the low resolution one
(EPI) as well, but the anatomical details are taken primarily from T2 image. On the fused image we perform fiber growth
between the two volumes of interest and we extract the fiber density (FD), fiber volume (FV) and fractional anisotropy
(FA). At this point, our approach differs from other fusion techniques because we are fusing the images at the information
level, using the registration for spatial alignment on the brain volume. We do not relay on prior atlases created for structural
MRI and no manual intervention is needed in the process2,3. Also we do not perform prior segmentation on white matter
(WM) and grey matter (GM) or use any maps for alignment and registration purposes4, 5.

PD prognosis

Contextual information

Prediction

H&Y value

CBIR

(Content-Based Image Retrieval)

Segmentation & Quantification

Fusion

Preprocessing

T2 image

EPI image

Extract anatomical VOI

Iconic based Registration

Extract tensor information

Fusion

CBIR

H&Y estimation

Fiber growth

Fiber image

FD

FV

FA

Fig. 1 PD early diagnosis / prognosis workflow chart

The information of each of the patients, after the fusion step, provides us with the quantitative data that we use for
classification prior to the CBIR step. Based on this classification, any new patient can be evaluated by performing a content
based image retrieval (CBIR) query in our indexed database. The query based on the quantification elements extracts all the
similar patients with the new one. The CBIR system registers the boundless of interests and taking the most similar patient
we compute an estimation of the Hohen&Yahr (H&Y) score for the new patient. This value allows us then to place the new
patient on the H&Y scale. As PD is detected only in advanced stage, our database contains mainly PD patients placed at
level 2 and 3. Using extrapolation functions we can deduce the evolution of the disease and predict the fiber values for the
level 1 and early PD patients.

Results: Our preliminary results are based on the correlation between the H&Y scores and the fiber attributes. For the
fiber density on the bundle of interest we have on both sides a correlation value obtained by the T-Test that is relevant
p=0.019 for the left side and p=0.015 for the right side. On the fiber volume for the left or right side p has the same value of
0.003. Also the volume of interest that contains the Substantia Nigra can be correlated with the H&Y scale and it gives us a
p value of 0.002 and 0.004 for the left side, respectively on the right side.

New breakthrough work: The main new breakthrough is represented by a method able to predict the PD, as well as
an evaluation method based on the image attributes, on the anatomical and neurological aspects of the patient. As the H&Y
test is based on the cognitive facet, our method is complementary to the test, but is placed on the same scale.

Conclusions: Our approach is important from the clinical point of view offering a new tool for the neurologists in PD and
a mean to verify/confirm their diagnosis and propose a prognosis. From the technical point of view, the fusion is new, as it
combines the tensor based information and the anatomical details. Another new aspect on this level is the use of CBIR
based on the quantification values, integrating a fiber-based registration. This step provides data for H&Y estimation and
PD prognosis.

Selective Bibliography:

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of brain donors” 15 March 2009, www.medicalnewstoday.com
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corticostriatal circuis in humans” ANN Neurol(2004); 55; 522-529, doi:10.1002/ana.20030
3. Vaillancourt, D. et al., “Imaging Technology May trace Development of Parkinson’s disease”, University of
Illinois at Chicago, Rush University, http://www.medicalnewstoday.com/articles/143566.php , 25 March 2009
4. Deisseroth, K. et al, “Stanford Study improves insight into Parkinson’s disease and possible treatments”, Stanford
University Medical Centre, http://www.medicalnewstoday.com/articles/143132.php , 22 March 2009
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2009.
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to 20.07.2009
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JNNP (2007); doi:10.1136/jnnp.2007.121525
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