High b-value q-space analyzed diffusion-weighted MRI using 1.5 tesla clinical scanner; determination of displacement parameters in the brains of normal versus multiple sclerosis and low-grade glioma subjects.
ABSTRACT We aimed to determine the displacement parameters in the brains of normal individuals relative to brain parenchymal abnormalities, such as multiple sclerosis (MS) and low-grade glioma, by q-space imaging (QSI) using 1.5-T magnetic resonance (MR) scanner.
Thirty-five normal, three pathologically proven low-grade glioma, and five MS subjects were imaged by a 1.5-T MR unit for QSI (b-values, 0-12,000 s/mm(2)). Mean displacement (MD) values in white matter (WM), gray matter (GM), and lateral ventricle (cerebrospinal fluid [CSF]) of normal subjects, plaques, and normal appearing WM (NAWM) of MS subjects and glioma lesions were calculated. Mann-Whitney U test was used for comparison.
In normal subjects, MD values were 6.6 ± 0.2, 8.44 ± 0.41, and 17.08 ± 0.80 μm for WM, GM, and CSF, respectively, while those for NAWM and WM plaques in MS, and glioma lesions were significantly higher at 7.0 ± 0.17, 9.3 ± 2.3, and 9.6 ± 0.40 μm, respectively, compared to WM in normal subjects.
We propose that the relative values of MD obtained by QSI in control and diseased tissues can be useful for diagnosing various WM abnormalities.
- [show abstract] [hide abstract]
ABSTRACT: We introduce and demonstrate an NMR pulsed gradient stimulated echo method of directly obtaining the molecular translational displacement probability (displacement profile) of a liquid. The temporal development of the displacement profile reflects the presence of diffusion, restrictions to diffusion (e.g., walls, membranes), flow, and spatially dependent relaxation sinks. This approach allows the study of compartments which are too small to be observed by conventional NMR imaging methods. The distribution of spatial properties of compartments can be characterized over a spatial field of about 0.1 to 25 microns, completely independent of the absolute spatial location of the individual compartments.Magnetic Resonance in Medicine 07/1990; 14(3):435-44. · 3.27 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Q-space analysis is an alternative analysis technique for diffusion-weighted imaging (DWI) data in which the probability density function (PDF) for molecular diffusion is estimated without the need to assume a Gaussian shape. Although used in the human brain, q-space DWI has not yet been applied to study the human spinal cord in vivo. Here we demonstrate the feasibility of performing q-space imaging in the cervical spinal cord of eight healthy volunteers and four patients with multiple sclerosis. The PDF was computed and water displacement and zero-displacement probability maps were calculated from the width and height of the PDF, respectively. In the dorsal column white matter, q-space contrasts showed a significant (P < 0.01) increase in the width and a decrease in the height of the PDF in lesions, the result of increased diffusion. These q-space contrasts, which are sensitive to the slow diffusion component, exhibited improved detection of abnormal diffusion compared to perpendicular apparent diffusion constant measurements. The conspicuity of lesions compared favorably with magnetization transfer (MT)-weighted images and quantitative CSF-normalized MT measurements. Thus, q-space DWI can be used to study water diffusion in the human spinal cord in vivo and is well suited to assess white matter damage.Magnetic Resonance in Medicine 05/2008; 59(5):1079-89. · 3.27 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which affects nearly one million people worldwide, leading to a progressive decline of motor and sensory functions, and permanent disability. High b-value diffusion-weighted MR images (b of up to 14000 s/mm(2)) were acquired from the brains of controls and MS patients. These diffusion MR images, in which signal decay is not monoexponential, were analyzed using the q-space approach that emphasizes the diffusion characteristics of the slow-diffusing component. From this analysis, displacement and probability maps were constructed. The computed q-space analyzed MR images that were compared with conventional T(1), T(2) (fluid attenuated inversion recovery (FLAIR)), and diffusion tensor imaging (DTI) images were found to be sensitive to the pathophysiological state of white matter. The indices used to construct this q-space analyzed MR maps, provided a pronounced differentiation between normal tissue and tissues classified as MS plaques by the FLAIR images. More importantly, a pronounced differentiation was also observed between tissues classified by the FLAIR MR images as normal-appearing white matter (NAWM) in the MS brains, which are known to be abnormal, and the respective control tissues. The potential diagnostic capacity of high b-value diffusion q-space analyzed MR images is discussed, and experimental data that explains the consequences of using the q-space approach once the short pulse gradient approximation is violated are presented.Magnetic Resonance in Medicine 02/2002; 47(1):115-26. · 3.27 Impact Factor
Clinical Investigative Study
High b-Value q-Space Analyzed Diffusion-Weighted MRI Using
1.5 Tesla Clinical Scanner; Determination of Displacement
Parameters in the Brains of Normal versus Multiple Sclerosis
and Low-Grade Glioma Subjects
Zareen Fatima, MBBS, Utaroh Motosugi, MD, PhD, Masaaki Hori, MD, PhD, Keiichi Ishigame, MD, PhD,
Toshiyuki Onodera, PhD, Kazuo Yagi, PhD, Tsutomu Araki, MD, PhD
From the Department of Radiology, University of Yamanashi, Yamanashi, Japan (ZF, UM, MH, KI, TA); Department of Radiology, School of Medicine, Juntendo University, Tokyo,
Japan (MH); and Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan (TO, KY).
Keywords: q-space imaging (QSI), nor-
mal brain, mean displacement (MD).
2010, and in revised form December 24,
2010. Accepted for publication February
Correspondence: Address correspon-
dence to Utaroh Motosugi, MD, PhD,
Department of Radiology, University of
Yamanashi, 1110 Shimokato, Chuo-shi,
Yamanashi 409-3898, Japan. E-mail:
J Neuroimaging 2011;XX:1-6.
A B S T R A C T
We aimed to determine the displacement parameters in the brains of normal individuals
relative to brain parenchymal abnormalities, such as multiple sclerosis (MS) and low-grade
glioma, by q-space imaging (QSI) using 1.5-T magnetic resonance (MR) scanner.
MATERIALS AND METHODS
Thirty-five normal, three pathologically proven low-grade glioma, and five MS subjects
were imaged by a 1.5-T MR unit for QSI (b-values, 0-12,000 s/mm2). Mean displacement
(MD) values in white matter (WM), gray matter (GM), and lateral ventricle (cerebrospinal
fluid [CSF]) of normal subjects, plaques, and normal appearing WM (NAWM) of MS subjects
and glioma lesions were calculated. Mann-Whitney U test was used for comparison.
In normal subjects, MD values were 6.6 ± 0.2, 8.44 ± 0.41, and 17.08 ± 0.80 μm
for WM, GM, and CSF, respectively, while those for NAWM and WM plaques in MS, and
glioma lesions were significantly higher at 7.0 ± 0.17, 9.3 ± 2.3, and 9.6 ± 0.40 μm,
respectively, compared to WM in normal subjects.
We propose that the relative values of MD obtained by QSI in control and diseased tissues
can be useful for diagnosing various WM abnormalities.
q-space imaging (QSI) is an advanced diffusion-weighted imag-
ing (DWI) technique. The inverse Fourier transformation of the
signal attenuation yields probability density function (PDF) of
the molecular displacement. These measurements enable us to
acquire information about cellular geometry in a noninvasive
manner (Figs 1A, 1B). Imaging is performed using multiple q-
values that express the diffusionsensitizationdefined as γδg/2π
in a reciprocal space known as q-space.1-3
Many studies have been conducted using q-space technique
to evaluate multiple sclerosis (MS)4-6vascular dementia,7ef-
fect of myelinization in animal models,8-10quantification of
axonal diameter, effects of hypertension and neuronal degen-
eration in excised rat spinal cord,11,12optic and sciatic nerves
of animals,13-15and in porous structures.16However, adequate
data for studying the parameters of QSI in normal subjects us-
ing a clinical scanner are lacking. We conducted this study to
determine the displacement parameters by QSI in brains of
normal individuals with an magnetic resonance (MR) scanner
used in clinical settings relative to those in MS and low-grade
glioma. This knowledge of normal displacement parameters is
extremely important and might form the foundation of future
applications of QSI for the evaluation of brain parenchymal
abnormalities that cause increased neuronal diffusibility.
Subjects and Methods
Thirty-five normal subjects, including 20 men and 15 women,
with a mean age (range) of 29.3 (13-45) years were selected
for the study out of the 350 imaged during the duration from
July 2008 to April 2010. Of the included subjects, 18 were vol-
unteers and 17 were patients who underwent brain MRI for
screening purposes and were found to have no radiological
or neurological abnormality. Five patients of MS, all women,
aged 21-38 years, and 3 patients with pathologically proven
C2011 by the American Society of Neuroimaging1
images (B) at the same level.
The figure shows the raw images at b-values from 0 to 12,000 s/mm2(A) and an MD map produced by processing of these raw
low-grade glioma, two men and one woman, aged 36-60 years,
were also included in the study. The pathological diagnoses
were astrocytoma (World Health Organization [WHO] grade
II) in 2 patients and oligoastrocytoma (WHO grade II) in 1 pa-
tion of gadolinium-based IV contrast agent. Written informed
consents were obtained from the participants and the study was
approved by the institutional review board.
The imaging was carried out with a 1.5 T Signa Excite HD
version 12, MR unit (GE Health Care, Milwaukee, WI, USA).
2 Journal of Neuroimaging Vol No 2011
The system provides a maximum gradient strength of 33 mT/m
and slew rate of 150 mT/m/ms. QSI was performed by using
a spin-echo diffusion-weighted echo-planar imaging sequence
with q gradients. The magnitude of the gradients was increased
in 12 equally spaced steps attaining a maximum b-value of
12,000 s/mm2and q-value of 838 cm−1. Other imaging param-
eters were ?/δ, 62/55.8 ms; TR/TE, 10,000/147.6 ms; matrix
128 × 128; field of view (FOV), 24 × 24 cm; and number of
excitation (NEX) = 1. The raw data comprised 20 axial images
each by applying the diffusion gradients along three orthogo-
nal axes at b-values of 1,000-12,000 s/mm2in 12 steps and 20
images at a b-value of 0 with a slice thickness/gap of 5 /1.5 mm,
constituting a set of 740 images. The total imaging duration was
6 minutes and 30 seconds.
Patients were also scanned according to the standard clin-
ical protocol with DWI, T1WI, T2WI, FLAIR sequence, and
T2∗WI, while only DWI and T2WI were performed in the nor-
mal volunteers. Postcontrast T1WI images were also obtained
in the patients with MS and glioma.
Raw QSI data were then transferred to another independent
computer and MD maps were obtained in each motion prob-
ing gradients (MPG) axis by using in-house interactive data
language (IDL)-based diffusion analysis software QSI Analyzer
2.4 developed by the Yagi laboratory at Tokyo Metropolitan
University, Tokyo, Japan, based on theory of q-space analy-
sis.17To obtain values of full width half maximum (FWHM)
of the centrum semiovale (WM), gray matter (GM), and cere-
of the same sizes (12 pixels for WM and 5 pixels for GM) were
carefully placed at the same locations in all cases by the same
radiologist (Fig 2). ROI were also placed in the lesions, that is,
plaque of MS and glioma in the WM (Figs 3A, 3B). The rules
for ROI placement in the lesions were as follows:
(1) The regions with high signal intensity on T2WI and FLAIR were
considered to be lesions.
(2) T2WI, FLAIR, and the raw image of QSI with b-value of 0 were
used as references.
(3) GM was excluded, even if the lesion extended into it.
In patients with MS, we also measured the molecular MD
of WM not showing high signal intensity on T2WI (normal
appearing WM [NAWM]).
The FWHM for each MPG direction, that is,, the x-, y-,
and z-axis, and then average of the three were calculated. MD
values were then calculated using the following equation:
MD =.425 FWHM.
Mann-Whitney U test was used to compare the mean dis-
placement (MD) of WM in normal subjects with those of the
plaque and NAWM in patients with MS and glioma lesions. A
two-sided P value of less than .05 was considered statistically
The MDs were 6.6 ± 0.2 μm for WM, 8.44 ± 0.41 μm for GM,
and 17.08 ± 0.80 μm for CSF in normal subjects.
Patients with MS
MDs of 7.0 ± 0.17 μm in NAWM and 9.3 ± 2.3 μm in WM
plaques were observed in these patients. MD of both NAWM
(P = .0011) and plaque (P < .0001) were significantly higher
than that of WM in normal subjects (Fig 4).
Fig 2. The figure depicts the location of ROI at white and gray matters in an MD map with a corresponding FLAIR image at the same level in
a normal subject.
Fatima et al: Determination of Normal Displacement Parameters in Brain by QSI3
lesion of glioma, taking FLAIR images at the same levels as references.
ROI have been placed on (A) a plaque of MS as well as in normal appearing white matter in a patient with multiple sclerosis and (B)
Patients with Low-Grade Glioma
The lesions of low-grade glioma were found to have an MD of
9.6 ± 0.4 μm, which was significantly higher than that of WM
in normal subjects (P < 0.0001) (Fig 4).
The principle behind the development of QSI was the quan-
tification of the restricted component. Clinical scanners cannot
fulfill the demands of the q-space theory due to their limitations
to produce high gradient amplitudes.18,19This in turn requires
long duration of gradient pulses, long diffusion time periods,
and thus long time to echo (TE) to attain high b- or q-values.
This results in an exaggeration of the restricted component and
in clinical scanners was proposed to be favorable for the detec-
tion of WM degenerative disorders due to increased sensitivity
to the restricted component.4,18
The MD obtained in our study was 6.6 ± 0.2 μm in the
white matter (WM). Assaf et al. observed an average MD of
approximately 2-4 μm in normal WM, 7-9 μm in GM, and
>10 μm in CSF in six normal subjects.6The MD in WM ob-
tained by Latt et al. was 9 μm in three normal subjects, which
was strikingly greater than previously reported observations.
Latt attributed the variation in results to the violation of the
short gradient pulse theory by Assaf et al., leading to underes-
timation of the MD values.19Such a violation was also present
in the QSI sequence used in this study, but the average MD
4Journal of Neuroimaging Vol No 2011
by high b-value q-space diffusion-weighted imaging technique in nor-
mal subjects versus multiple sclerosis and low grade glioma. One of
the MS plaques had higher value of mean displacement beyond the
selected scale and is shown along with its value (13.3 μm) as highest
mark in this category.
Scatter plot displays mean displacement values calculated
was quite different from the earlier study. Second, experimen-
tal studies have revealed that the use of longer δ results in
smaller MD values by q-space analysis, but this change is not
To our understanding, the resolution of the distribution
displacement profile is a possible contributing factor in these
variations. The resolution of QSI is dependent upon the maxi-
mal q-value, number of diffusion gradients, and the difference
in q-values between two adjacent diffusion gradients (?q).3
FWHM values are highly dependent upon the resolution.
The spatial resolution achieved by Assaf et al.6was approxi-
mately 4 μm, while that used by Latt et al.19was 11 μm. The
spatial resolution of our QSI measurements is 11.9 μm. This
resolution is insufficient to measure the displacements in a bi-
ological environment and might be an important cause of the
overestimation of MD and seems to be the cause of the higher
values obtained in our study. This difference is more promi-
nent in WM where the MD values calculated by Assaf et al. are
much smaller than ours and are beyond the resolution capacity
of QSI sequence used by us, while in GM, the values are quite
similar 8.8 μm in present study compared to 7-9 μm, thus also
altering the ratio of MD in GM to WM.
MD values obtained in the MS plaques as well as in NAWM
were significantly higher than those obtained in normal individ-
uals. Increased diffusivity in the MS plaques is apparently due
to myelin degradation and thus loss of confining barriers lead-
ing to higher values of MD. Likewise, as is already known that
WM hyper intensities on FLAIR and T2WI do not show the
true extent of the disease and variable degrees of postmortem
histopathological changes have been noted in the areas that
did not show any abnormality on these sequences. QSI is ex-
tremely sensitive even for detecting the abnormalities present
in NAWM,4,6as also noted in our study showing a significant
difference in MD values relative to WM in control subjects.
Similarly, the low-grade gliomas are known to have a mod-
erate cellular density of the tumor cells.22It obviously disrupts
the normal architectural anatomy of the brain parenchyma,
leading to loss or displacement of myelinated fibers, which in
turn increases the local area of increased diffusivity.23
Our study had some limitations such as smaller sample size
for patients having MS and low-grade glioma. One of the pa-
tients havinglow-grade glioma aged 60years thatdidnot match
the ages of other subjects and was also a drawback as the WM
diffusibility changes are also expected with advancing age due
to decreased myelination. Single averaging of the signals would
provide limited signal-to-noise ratio especially on ultra-high b-
value images, for example, b = 10,000 or 12,000 s/mm2, which
is also a limitation of our study. Low signal-to-noise ratio at high
b-value images might affect the calculated MD. It might be a
cause of concern about the reliability of the absolute values in
our study. However, we still believe that this study would be
a guide for the future studies on QSI for its clinical applica-
tion, using higher magnetic field MR unit such as 3-tesla or
In conclusion, acceptable values of MD may be obtained by
QSI using a clinical scanner, despite violation of short gradient
pulse theory, and this technique can be employed clinically to
detect the extent of changes in MD due to WM pathologies, in-
cluding MS and low-grade glioma relative to the normal values
in the particular settings.
1. Cory DG, Garroway AN. Measurement of translational displace-
ment probabilities by NMR: an indicator of compartmentation.
Magn Reson Med 1990;14:435-444.
2. Callaghan PT, MacGowan D, Packer KJ, et al. High resolution q-
space imaging in porous structures. J Magn Reson 1990;90:177-182.
3. Cohen Y, Assaf Y. High b-value q- space analyzed diffusion-
weighted MRS and MRI in neuronal tissues- a technical review.
NMR Biomed 2002;15:516-542.
4. Assaf Y, Chapman J, Ben-Bashat D, et al. White matter changes
in multiple sclerosis: correlation of q- space diffusion MRI and H
MRS. Magn Reson Imaging 2005;23:703-710.
5. Farrell JAD, Smith SA, Gordon-Lipkin EM, et al. High b-value q-
space diffusion-weighted MRI of the human cervical cord in vivo:
feasibility and application to multiple sclerosis. Magn Reson Med
6. Assaf Y, Ben-Bashat D, Chapman J, et al. High b-value q-space
analyzed diffusion-weighted MRI: application to multiple sclerosis.
Magn Reson Med 2002;47:115-126.
7. Assaf Y, Mayzel-Oreg O, Gigi A, et al. High b value q-space-
analyzed diffusion MRI in vascular dementia: a preliminary study.
J Neurol Sci 2002;203-204:235-239.
8. Assaf Y, Mayk A, Cohen Y. Displacement imaging of spinal
cord using q-space diffusion-weighted MRI. Magn Reson Med
9. Biton IE, Duncan ID, Cohen Y. High b-value q-space diffusion
MRI in myelin-deficient rat spinal cords. Magn Reson Imaging
10. Bar-Shir A, Duncan ID, Cohen Y. QSI and DTI of ex-
cised brains of the myelin-deficient rat. Neuroimage 2009;48:109-
11. Ong HH, Wright AC, Wehrli SL, et al. Indirect measurement
of regional axon diameter in excised mouse spinal cord with q-
space imaging: simulation and experimental studies. Neuroimage
Fatima et al: Determination of Normal Displacement Parameters in Brain by QSI5
eration in excised rat spinal cord studies by high b-value q-space
diffusion magnetic resonance imaging. Exp Neurol 2003;184:726-
13. Ronen I, Kim D. Compartment-specific q-space analysis of
diffusion-weighted data from isolated rhesus optic and sciatic
nerves. Magn Reson Imaging 2009;27:531-540.
14. Assaf Y, Cohen Y. Structural information in neuronal tissue as
revealed by q-space diffusion NMR spectroscopy of metabolites in
bovine optic nerve. NMR Biomed 1999;12:335-344.
15. Bar-Shir A, Cohen Y. High b-value q-space diffusion MRS of
nerves: structural information and comparison with histological
evidence. NMR Biomed 2008;21:165-174.
16. Topgaard D, S¨ oderman O. Experimental determination of pore
time limit. Magn Reson Imaging 2003;21:69-76.
by 3D diffusion-weighted MRI. Magn Reson Imaging 2008;26:437-
18. Yeh CH, Tournier JD, Cho KH, et al. The effect of finite diffusion
gradient pulse duration on fiber orientation estimation in diffusion
MRI. Neuroimage 2010;51:743-751.
19. Latt J, Nilsson M, Wirestam R, et al. In vivo visualization of
displacement-distribution- derived parameters in q-space imaging.
Magn Reson Imaging 2008;26:77-87.
architecture with diffusion spectrum magnetic resonance imaging.
Magn Reson Med 2005;54:1377-1386.
21. Mitra PP, Halperin BI. Effects of finite gradient-pulse widths in
pulsed-field-gradient diffusion measurements. J Magn Reson ser A
22. Van Veelen ML, Avezaat CJ, Kros JM, et al. Supratentorial low
grade astrocytoma: prognostic factors, dedifferentiation, and the
issue of early versus late surgery. J Neurol Neurosurg Psychiatry
23. Witwer, BP, Moftakhar R, Hasan KM, et al. Diffusion-tensor imag-
ing of white matter tracts in patients with cerebral neoplasm.
J Neurosurg 2002;97:568-575.
6 Journal of Neuroimaging Vol No 2011