Optimization Of B Value For Diffusion Tensor Imaging Biology Essay

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Recently, several studies on diffusion tensor imaging of the median nerve have been published. However, various imaging and reconstruction parameters were used. The purpose of this study was to systematically assess the optimal b-value for DTI and fiber tractography of the median nerve at 3.0T as well as optimal reconstruction parameters for fiber tractography.

1.2. Materials and methods

This is a prospective study carried out with local ethical board approval and written informed consent from all study subjects. 45 healthy volunteers (15 men, 30 women; mean age, 41±3.4 years) underwent diffusion tensor imaging of the right wrist at 3.0T (Achieva X-series, Phillips, Best, the Netherlands) using an 8-channel wrist coil (Achieva Sense, Philips, Best, the Netherlands). A single-shot echo-planar-imaging sequence (TR/TE 10123/40ms) was acquired from each subject at four different b-values (800, 1000, 1200, and 1400 s/mm2).

Post processing and Fiber-tractography was performed by two independent readers using dedicated Software (Philips Achieva Version.X.X, Best, the Netherlands). FA, ADC and color-coded diffusion maps were calculated and fiber tracts were generated using four different fiber tractography algorithms containing different FA thresholds and different reconstruction angles.

Fiber tractography was then evaluated quantitatively and qualitatively.

1.3. Results

Fiber tractography generated significantly longer fibers in DTI acquisitions with higher b-values (1200 and 1400 s/mm2) compared to acquisitions with b-values of 800 and 1000 s/mm2 (p<0.001). The overall quality of fiber tractography (fiber length, homogeneity, density and accordance with anatomy) was best at a b-value of 1200 s/mm2 (p<0.001). The tracking algorithm using a minimum FA threshold of 0.2 and a maximum angulation of 10° was significantly better than all other reconstruction algorithms.

1.4. Conclusion

At 3.0T, the optimal b-value for DTI is 1200 s/mm2 and the optimal reconstruction parameters for fiber tractography are a minimum FA threshold of 0.2 and a maximum reconstruction angle of 10°.

2. Introduction

Recently, several pilot studies regarding the application of diffusion tensor imaging (DTI) and fiber tractography to peripheral nerves (e.g., the median, radial, and ulnar nerve in the wrist, the peroneal and tibial nerve in the knee/calf/ ankle, as well as the sciatic nerve) have been published. Possible clinical applications include the evaluation of peripheral nerves in compressive neuropathies such as the carpal tunnel syndrome (CTS) or tracking of peripheral nerves in the presence of malignant neoplasm.(1-7)

DTI is based on magnetic resonance imaging (MRI) and reveals micro structural characteristics of biological tissues by observing the random movement of water molecules (Brownian motion). DTI is especially advantageous for tissues containing highly organized microstructures (e.g. cell membranes, vascular structures or axon cylinders), given that in these tissues water can not freely diffuse in all directions. This inhomogeneity of diffusion is called anisotropy and can be quantified with DTI.(8-11)

To obtain diffusion-weighted images, a pair of strong gradient pulses is added to the pulse sequence. The first pulse dephases the spins, and the second pulse rephases the spins. If the spins move between the gradient pulses, rephasing will be incomplete and the image will show a signal-attenuation proportional to the amount of water diffusion in the specific orientation of the applied magnetic field gradients in three-dimensional space.(1, 12-14)

The diffusion-weighted images obtained with at least six different diffusion gradient orientations can be used to calculate a tensor (e.g. a 3 x 3 matrix). The main diffusion direction will be indicated by the tensor's main eigenvector. Quantitative diffusion metrics such as maps for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and color-coded diffusion maps, as well as fiber tractography can then be computed.

ADC is a measure of diffusion magnitude, describing mean diffusivity. FA is a scalar parameter, describing the degree of anisotropy. FA is scaled to obtain values between 0 and 1; 0 representing random isotropic diffusion and 1 representing complete anisotropy. In color-coded maps the directional components of the principal eigenvector are assigned to different colors (typically red, green, and blue). The resulting image is weighted with the FA map to exclude tissues with isotropic diffusion. Fiber tractography is a line propagation method used to visualize DTI data. Anisotropic structures such as nerves or nerve bundles can be tracked and displayed on color-coded three-dimensional images. The most commonly used fiber tracking method is, to propagate a line from a seed point by following the local vector orientation. For fiber tractography various reconstruction parameters have been used in the past literature.(1, 8, 14)

DTI is a well established technique in the central nervous system, yet its application to the peripheral nervous system is challenging presumably because in most other tissues water proton density is lower than in the central nervous system. The primary parameter determining the sensitivity in a diffusion-weighted sequence is described by the b-value, a user defined parameter proportional to the amplitude and duration of the diffusion-sensitizing gradients. Increasing b-values reflect increasing diffusion weighting of a DTI acquisition but do also lead to a lower signal-to-noise ratio (SNR).(1, 3-6, 12, 15)

To the best of our knowledge, so far there has only been one report, regarding the systematical evaluation of the optimal b-value for DTI of peripheral nerves.(1) This study however was performed using a 1.5T MR unit. At present, data for higher field strengths (i.e. 3.0T) are still not available in the literature. Yet the optimal b-value for 3.0T is expected to be different than for 1.5T, since 3.0T MR units usually offer stronger gradient systems in addition to a much higher SNR.

Thus, the purpose of this study was to systematically assess the optimal b-value for DTI and fiber tractography of the median nerve at 3.0T as well as optimal reconstruction parameters for fiber tractography.

Please note: For further information on MR imaging physics, T1- and T2-weighted and diffusion weighted MR imaging as well as tractography, please refer to the Appendix.

3. Materials and methods

3.1. Study subjects

This is a prospective cross-sectional study with prior approval by the institutional review board (IRB approval number (KEK-ZH-Nr.), 2009-0133/5). This study was conducted according to the Helsinki declaration with written informed consent obtained from all study subjects.

Between April and June 2010, 45 healthy volunteers were included in this study (15 men, 30 women; median age, 39 years; mean age, 41±3.4 years; age range, 22-66 years). Inclusion criterion was age >18. Exclusion criteria were general contraindications for MRI (e.g. pacemaker), pregnancy, history of prior surgery and cardiovascular, pulmonary, endocrine, metabolic, neurological, neuromuscular, or musculoskeletal disorders. All 45 subjects underwent MRI of the right wrist. All subjects were right-handed.

3.2. MR imaging

All MR images were acquired with a 3.0T MRI scanner (Achieva X-series, Philips, Best, the Netherlands), using an eight channel wrist coil (Achieva Sense, Philips, Best, the Netherlands). This MRI system allows field gradient amplitudes up to 80 mT/m, or slew rates up to 200 mT/m/s.

The wrist coil was positioned in the center of the magnet bore, since previous studies achieved a significantly better quality of the echo-planar images, compared to a lateral position, commonly used for anatomical imaging.(5) All imaging was performed with subjects placed in the scanner in prone position, with their right hand extended over the head ("superman" position).

The study protocol included a standard T1 weighted turbo spin echo (TSE) MR sequence (repetition time (TR)/ echo time (TE), 636/21 ms; matrix size, 400 x 264 mm; field of view (FOV), 120 x 80 mm; acquisition voxel size 0,3 x 0,3 x 4 mm; reconstructed voxel size 0,15 x 0,15 x 4 mm; number of slices, 25; TSE factor 3; number of signal acquisitions (NSA) 1; sense factor 2; acquisition time, 4:38 min) that was used as anatomical reference. In addition, four spin-echo-based single-shot echo-planar imaging (EPI) MR sequences (TR/TE, 10123/40 ms; matrix size 100 x 82 mm; FOV 120 x 99 x 100 mm; acquisition voxel size 1,2 x 1,2 x 4 mm; reconstruced voxel size 0,54 x 0,54 x 4 mm; number of slices 25; NSA 2, fat suppression SPAIR; EPI factor 45; sense factor 2, acquisition time 6:06 min) with diffusion sensitizing gradients were performed in each subject using four different b-values 800, 1000, 1200 and 1400 s/mm2. Each acquisition included 15 different diffusion gradient orientations, distributed evenly to the surface of the unit sphere. Prior to the DTI acquisition, high-order shimming with a XX-cm FOV was applied to reduce inhomogeneities of the main magnetic field in the imaging area. Slice location and all other image parameters were kept identical in all acquisitions.

3.3. Post-processing and fiber tractography

For calculations, measurements and fiber tractography, all images were transferred to an independent workstation and post-processed by two independent readers (P.E., D.M.; both readers were trained in post-processing DTI data) using dedicated Software (Philips Achieva Version.X.X, Best, the Netherlands).

First, ADC maps, FA maps, and color-coded diffusion maps, were calculated. Then, FA and ADC values were measured within a specific region of interest (ROI) containing the nerve fibers of interest (ROI technique). Measurements were done at three different transaxial levels defined by the following anatomical structures: distal radioulnar joint, pisiform bone and hamate bone. The standard T1-weighted TSE sequence was used as an anatomical reference to ensure the proper placement of the ROIs on the FA and ADC maps. Size, shape and location of the ROIs were kept identical for all measurements in the four different b-value acquisitions of each study subject.

Fiber-tractography was performed by choosing three initial seed ROIs through which the fibers were tracked. A freehand ROI was positioned in the FA and color-coded maps at the same three transaxial levels as mentioned above. The seed ROIs for fiber-tractography were slightly larger than the actual cross-sectional area of the median nerve, in order to include all nerve fibers. Care was taken not to include any relevant surrounding anatomical structures (e.g., vessels or tendons). Based on previous literature, four different fiber reconstruction algorithms containing two different FA threshold values (0.2 / 0.3) and two different angulation tolerances (10° / 20°) were chosen as reconstruction parameters. Fiber tracking was terminated if FA values were below the selected threshold or if fiber angulation exceeded the selected tolerance angle.

Overall, a total of 720 fiber tract images were generated (4 b-value acquisitions x 4 fiber reconstruction algorithms x 45 study subjects = 720 fiber tract images). All fiber tract images were electronically stored on the workstation for a subsequent qualitative evaluation.

3.4. Quantitative and qualitative analysis

The quantitative and qualitative analysis was performed by the same two independent authors who post-processed the DTI datasets.

Criteria for qualitative evaluation included fiber tract homogeneity, fiber tract density, fiber length and the fiber tracts accordance to anatomy. The stored fiber tract images were presented in random order. Both readers were blinded to the corresponding b-values and the personal data of the subject. Both readers ranked the image quality in consensus using a four point rank scale (from 4 = best to 1 = worst).

3.5. Statistical analysis

All calculations were performed by two authors (P.E., R.G.) using Excel® (release 14.0, Microsoft, Redmond, WA, USA) and SPSS® (release 18.0, SPSS Inc., Chicago, IL, USA)

…

4. Results

Fiber tractography generated significantly longer fibers in DTI acquisitions with higher b-values (1200 and 1400 s/mm2) compared to acquisitions with b-values of 800 and 1000 s/mm2 (p<0.001). The overall quality of fiber tractography (fiber length, homogeneity, density and accordance with anatomy) was best at a b-value of 1200 s/mm2 (p<0.001). The tracking algorithm using a minimum FA threshold of 0.2 and a maximum angulation of 10° was significantly better than all other reconstruction algorithms.

…

5. Discussion

Study Subjects (Male Female)

At 3.0T, the optimal b-value for DTI is 1200 s/mm2 and the optimal reconstruction parameters for fiber tractography are a minimum FA threshold of 0.2 and a maximum reconstruction angle of 10°.

Signal to Noise Ratio

Best tracking parameters

Potential clinical use

Limitations: distortion artifacts, SNR, Software dependency

6. Appendix

6.1. Physics of MR Imaging

An MR image represents the relative response of biological tissues to absorbed radio frequency energy. Usually MR imaging observes the nuclei of hydrogen atoms because of the relative abundance of water in the human body. Their distribution and characteristic properties vary depending on their physical and chemical environment. Depending on the observed parameters various types of contrast can be generated. This makes MR imaging a very versatile technique.(9, 16, 17)

A hydrogen atom consists of a nucleus containing a single proton with a positive charge and of a single electron with a negative charge orbiting the nucleus. Any nucleus with an uneven atomic mass or uneven atomic number possesses the intrinsic quantum property of spin, according to the Pauli Exclusion Principle. As a charged particle with spin, the nucleus induces a corresponding magnetic field, making it a magnetic dipole. Normally, at room temperature without the presence of an external magnetic field, the magnetic orientation of a collection of hydrogen nuclei (protons) will be randomly distributed according to the principles of Brownian motion.(18-20) However when an outer magnetic field B0 is applied, the protons will tend to assume magnetic orientations either parallel or anti-parallel to the outer magnetic field, slightly favoring the parallel orientation, equivalent to the low energy state. Thus, the sum of their magnetic dipole moments results in a small net magnetization vector parallel to the outer magnetic field. Inconsistencies in the alignment of the protons magnetic orientation with the outer magnetic field let the spin vectors of the protons experience a torque, causing their precession around the outer magnetic field's longitudinal axis with a specific frequency proportional to the strength of the outer magnetic field. This frequency is called the Larmor frequency and is described by the Larmor equation:

ω (frequency) = γ (gyro-magnetic ratio constant) B0 (outer magnetic field)

The sum of the precession-equivalents of all water protons is the signal (electric current in a receiver coil) measured in MR imaging. Larmor precession is a resonance phenomenon, allowing a transfer of energy to the precessing protons by a radiofrequency (RF) pulse of the same frequency. Prior to an RF pulse, the net magnetization vector is aligned parallel to the main magnetic field B0 and the longitudinal axis. As energy is absorbed from an applied RF pulse, the net magnetization vector rotates away from the longitudinal direction. The amount of rotation (called the flip angle) depends on the strength and duration of the RF pulse.

A 90° RF pulse rotates the net magnetization into the transverse plane. A 180° RF pulse rotates the net magnetization by 180° into the opposite direction.(16, 21)

6.2. T1- and T2-weighted images

T1 relaxation is defined as the rate at which net magnetization realigns with the longitudinal direction after a 90° RF pulse rotates is applied. The definition of T1 is the time elapsed until the longitudinal magnetization to reaches 63% of its final value, assuming a 90° RF pulse. Different tissues have different rates of T1 relaxation. If an image is acquired while T1 relaxation curves are widely separated, T1-weighted contrast will be maximized.

T2 relaxation occurs when spins in the high and low energy state exchange energy but do not loose energy to the surrounding lattice.

T2* is characterized by B0 inhomogeneity and loss of transverse magnetization at a rate greater than T2.

T2 relaxation can be explained by a loss of coherence or synchrony of the protons. During an RF pulse, the protons precess in phase. After a 90° RF pulse, the phases of the protons desynchronize because each proton precesses at a slightly different speed due to various effects such as spin-spin interactions or local inhomogeneities of the magnetic field. What observed is, is the vector sum of all phases; a loss of synchronization of the phases leads to the loss of signal in MR imaging. T2 relaxation is defined as the time elapsed until the transverse magnetization decays to 37% of its original value. Different tissues have different rates of T2 relaxation. T2 weighting is obtained by inserting a weighting period between the 90° RF pulse and data acquisition. This time period is called echo time (TE). If TE is increased, T2-weighted contrast will be maximized.

The exact mechanism leading to longer or shorter T2 relaxation is not completely understood. T2 relaxation times seem to be prolonged in environments where water protons can freely tumble (e.g., less viscosity or fewer macromolecules with which to interact). Thus fluids have the longest T2s (700-1200 ms), and water based tissues are in the 40-200 ms range, while fat based tissues are in the 10-100 ms range.

T2 weighted images in MRI are often thought of as "pathology scans" because collections of abnormal fluid appear brighter against the darker normal tissue. A typical example is the formation of edema, leading to a significantly prolonged T2-weighted signal.

T1 and T2 relaxation processes occur simultaneously After a 90° RF pulse, dephasing of the transverse magnetization occurs while the longitudinal magnetization is restituted but T2 decay occurs 5 to 10 times more rapidly than T1 recovery. After a few seconds, most of the transverse magnetization will be dephased and most of the longitudinal magnetization will be restituted.(9)

6.3. Diffusion MR Imaging

In an isotropic environment, such as cerebrospinal fluid, water molecules diffuse freely at equal rates of approximately 0.1 mm/sec in all directions. In tissues containing highly organized microstructures (e.g. cell membranes, vascular structures or axon cylinders) water molecules can not freely diffuse in all directions, but preferably diffuse in the direction aligned with the internal structure. This inhomogeneity of diffusion is called anisotropy.(22)

It has been long, but not widely known that MR imaging is capable of quantifying diffusional movement of molecules using diffusion-weighted imaging (DWI) techniques, as described by Stejskal and Tannner in1965.(23) In 1985 LeBihan integrated the diffusion weighting technique developed by Stejskal and Tanner into MR Imaging. The first important clinical application of DWI was the detection of stroke in its acute phase. As anisotropic water diffusion in highly ordered tissues, such as the brain, had been observed, Basser, Mattliello and LeBihan established DTI in the 1990s, which became a widely used technique(8-11)

In DTI, each voxel is defined by a rate of diffusion and a preferred direction of diffusion in three dimensional space. To obtain diffusion-weighted images, a pair of strong gradient pulses is added to the pulse sequence. After the first gradient pulse is applied, protons start to precess at different rates, depending on their location in the gradient field. In analogy to T2 relaxation, these differences in the precession rate lead to dispersion of the phase and signal loss. However, if an identical gradient pulse of opposite magnitude is subsequently applied, protons can be refocused or rephrased. The refocusing will not be perfect for protons that have moved between the two gradient applications. Thus, the measured signal is reduced. This way an acquisition is sensitized to motional processes such as flow or diffusion in a specific direction. The primary parameter determining sensitivity in a diffusion-weighted sequence is described by the b-value. This parameter is proportional to the slope and duration of the diffusion-sensitizing gradients.

In order to measure a tissue's complete diffusion profile, repeated scans with different directions of the diffusion sensitizing gradients are required. For DWI three gradient-directions are normally sufficient to estimate the average diffusivity. Clinically, so called trace-weighted images are used to diagnose vascular strokes in the brain, by early detection of hypoxic edema. For DTI however, the properties of each voxel are usually calculated by vector or tensor math from six or more different diffusion weighted acquisitions, significantly increasing acquisition time. The main diffusion direction will be indicated by the tensor's main eigenvector. In color-coded maps the directional components are assigned to different colors (typically red, green, and blue). The resulting image is weighted with the FA map to exclude tissues with isotropic diffusion. FA is a scalar parameter, describing the degree of anisotropy. FA is scaled to obtain values between 0 and 1; 0 representing random isotropic diffusion and 1 representing complete anisotropy. ADC is a measure of diffusion magnitude, describing mean diffusivity.DTI is a relatively simple model of the diffusion process, assuming homogeneity and linearity of diffusion within each image voxel, resulting in a single tensor-ellipsoid per voxel.

Recently, more advanced models of the diffusion process have been proposed that aim to overcome the weaknesses of the diffusion tensor model (e.g. crossings of nerves) Amongst others, these include q-space imaging and generalized diffusion tensor imaging. (1, 8, 12-14, 20, 21, 24-28)

6.4. Tractography

The directional information of a DTI acquisition can be exploited to perform tractography in anisotropic tissues. Fibrous structures such as nerves or nerve bundles can be tracked and displayed on color-coded three-dimensional images. The most commonly used fiber tracking method is, to propagate a line from a seed point by following the local vector orientation.

Moseley presented an abstract with the first tractogram in 1992. Further advances in the development of tractography can be accredited to Mori, Pierpaoli, Lazar, Conturo and many others.(1, 8, 14)

Echo planar imaging

In single-shot echo-planar imaging, all spatial-encoding data of an image can be obtained after a single radio-frequency excitation. Echo-planar imaging offers major advantages over conventional MR imaging, such as reduced imaging time, decreased motion artifacts, and the possibility to image rapid physiologic processes in the human body.

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