Phase unwrapping of MR images using ΦUN
Transcription
Phase unwrapping of MR images using ΦUN
Medical Image Analysis 13 (2009) 257–268 Contents lists available at ScienceDirect Medical Image Analysis journal homepage: www.elsevier.com/locate/media Phase unwrapping of MR images using UUN – A fast and robust region growing algorithm Stephan Witoszynskyj a,d,*,1, Alexander Rauscher a,c,1, Jürgen R. Reichenbach a, Markus Barth b a Medical Physics Group, Institute for Diagnostic and Interventional Radiology, Friedrich Schiller University, Jena, Germany Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands c MRI Research Centre, University of British Columbia, Vancouver, Canada d Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria b a r t i c l e i n f o Article history: Received 25 July 2007 Received in revised form 31 July 2008 Accepted 13 October 2008 Available online 18 October 2008 Keywords: MRI SWI Field maps Phase imaging a b s t r a c t We present a fully automated phase unwrapping algorithm (UUN) which is optimized for high-resolution magnetic resonance imaging data. The algorithm is a region growing method and uses separate quality maps for seed finding and unwrapping which are retrieved from the full complex information of the data. We compared our algorithm with an established method in various phantom and in vivo data and found a very good agreement between the results of both techniques. UUN, however, was significantly faster at low signal to noise ratio (SNR) and data with a more complex phase topography, making it particularly suitable for applications with low SNR and high spatial resolution. UUN is freely available to the scientific community. Ó 2008 Elsevier B.V. All rights reserved. 1. Introduction Magnetic resonance data are complex numbers, but most often only magnitude images are reconstructed. However, phase information can be extremely valuable. For example, phase is very sensitive to small deviations from the resonance frequency that can be induced by inhomogeneities of the magnetic field. It is thus essential for susceptibility weighted imaging (SWI) (Reichenbach et al., 1997), phase imaging of the human brain (Ogg et al., 1999; Barth et al., 2003; Rauscher et al., 2005; Duyn et al., 2007; Koopmans et al., 2008) and the calculation of field maps (Johnson and Hutchison, 1985; Jezzard and Balaban, 1995). Other applications that utilize phase information include phase contrast angiography (Bryant et al., 1984) or MR elastography (Kruse et al., 2000) where the movement of magnetic moments leads to phase offsets. Phase images can also facilitate the segmentation of tissues (Bourgeat et al., 2007). In all these applications, a physical quantity is mapped into the phase’s limited domain (p 6 / < p or 0 6 / < 2p depending on the definition). This mapping can cause aliasing. In the literature, the resulting ambiguities are usually referred to as phase wraps. * Corresponding author. Address: Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel.: +43 1 40 400 5751; fax: +43 1 40 400 4898. E-mail addresses: [email protected], stephan.witoszynskyj@ gmx.at (S. Witoszynskyj). 1 Both authors contributed equally. 1361-8415/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.media.2008.10.004 Although the true value of the phase cannot be known unless additional assumptions are made, the elimination of phase wraps (i.e. phase unwrapping) often is required before any further postprocessing steps can be applied. The problem of phase unwrapping arises in various fields, ranging from optics, over radar interferometry, to MRI. Especially in the case of two- or higher dimensional data it is a non trivial task. In MRI, there are several situations in which phase unwrapping can be circumvented. For example field maps can be calculated by computing the arc-tangent of a complex division of two gradient echo scans acquired at different echo times. Nevertheless, phase wraps may remain in areas affected by strong field inhomogeneities (Cusack and Papadakis, 2002; Hutton et al., 2002). Homodyne detection (Noll et al., 1991) is a technique that removes phase variations with low spatial frequencies and thus reduces the likelihood of phase wraps. It is often used in situations where phase information of a single high-resolution scan is needed (e.g. SWI (Reichenbach and Haacke, 2001)). However, it is unsuitable for methods, such as field mapping (Jezzard and Balaban, 1995) or simulations of signal loss based on phase images (Rauscher et al., 2006), that depend on knowledge of all spatial frequencies of the phase. Furthermore, residual phase wraps may remain. These remaining phase wraps may have singularities which impede any true phase unwrapping. Completely eliminating phase wraps without suppressing valuable information is often impossible. In particular, if very long echo times are used to achieve good susceptibility contrast in phase imaging (Ogg et al., 1999; Barth 258 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 et al., 2003; Rauscher et al., 2005; Duyn et al., 2007), homodyne filtering fails in areas with background field inhomogeneities. A number of different approaches to true phase unwrapping can be found in the literature (e.g. Hedley et al., 1992; An et al., 2000, 2002; Jenkinson, 2003; Volkov and Zhu, 2003; Xu and Cumming, 1999). Although much effort has been made to obtain correctly unwrapped phase images, execution times are seldom reported. However to be useful for applications, an algorithm must not only be stable and robust but its implementation must result in unwrapped phase images within an acceptable time. This is especially true for SWI which is based on high-resolution data. While matrix sizes of 128 64 and a slice thickness of 3 mm can be sufficient for field mapping to correct for distortions in EPI (Windischberger et al., 2004), typical SWI data-sets can have matrix sizes of 512 384 96. This increase in data size by about two orders of magnitude makes fast processing rather critical. Furthermore, in some applications, such as SWI in general, but also in EPI-based fMRI (Robinson et al., 2004; Poser et al., 2006) and especially in contrast-enhanced SWI (CE-SWI) with SPIO, areas with reduced signal are of interest (Dahnke and Schaeffter, 2005; Hamans et al., 2006). Phase information is still available in those regions. Thus, a phase unwrapping algorithm useful for these applications must perform well in low SNR areas. Xu and Cumming presented an algorithm for the unwrapping of synthetic aperture radar (SAR) interferograms, which are known to have areas of both low phase SNR and high density of phase wraps (Xu and Cumming, 1999). Their method was shown to venture deep into noisy areas and the application to SWI data (Rauscher et al., 2003) leads, in principle, to satisfactory results. Nevertheless, in areas of steep phase topography or ghosts, the performance of this method is suboptimal, because only the local coherence of the phase is considered. Our goal was thus to extend this promising approach such that it exploits additional information available in MRI to make it better suitable for MRI data. This was done by optimizing the criteria for placing seed points and for guiding the unwrapping. We put a strong emphasis on a fast implementation that would be suitable for large SWI data-sets. In this paper we present our modified region growing phase unwrapping method. The emphasis of our approach was to develop a method that is suitable for high-resolution applications that can be affected by areas of very low SNR. As mentioned before, this demands high performance in terms of speed and reliable prediction of the unwrapped phase. For evaluation we compared an implementation of our approach to a well established method namely PRELUDE (Jenkinson, 2003) which is part of the FSL Analysis Package. The implementation of our method is freely available to the research community and can be obtained from the authors. 2. Theory 2.1. Problem definition Let’s assume a 2D complex MR image of dimensions Nx Ny. ^i;j reflect the The real and imaginary signal component of a pixel p x and y components of the magnetization vector in the rotating frame of reference (Haacke et al., 1999). The pixel’s complex value can also be represented by its magnitude qi,j and phase /i,j: ^i;j ¼ qi;j ðcos /i;j þ i sin /i;j Þ ¼ qi;j ei/i;j : p ð1Þ It is apparent that /i,j is ambiguous. If the phase corresponds to a physical quantity f we can write /i;j ¼ W½fi;j ; ð2Þ where W is the wrapping operator that projects f into the domain of the phase /. Phase unwrapping tries to regain the information that is lost by applying the wrapping operator. The ‘‘true” phase can be written as /ui;j ¼ /i;j þ 2pmi;j : ð3Þ Unwrapping the phase corresponds to finding the correct mi,j, which can be difficult in the presence of noise. 2.2. Phase unwrapping by region growing We base our work on a region growing phase unwrapping algorithm originally developed for SAR interferometry (Xu and Cumming, 1999). This method calculates a phase prediction /pi;j for each pixel in the immediate neighborhood of a region of pixels that have been unwrapped in previous iterations. The prediction /pi;j is the average of a number of individual predictions /pi;j;i0 ;j0 where (i0 , j0 ) 2 N(i, j). N(i, j) denotes already unwrapped immediate neighbors of (i, j). The predictions /pi;j;i0 ;j0 are computed by linear extrapolation from the next nearest neighbor if the next nearest neighbor has already been unwrapped. If the next nearest neighbor has not been unwrapped /pi;j;i0 ;j0 is set to the unwrapped phase /ui0 ;j0 of (i0 , j0 ). A pixel (i, j) is unwrapped and added to a region if it passes the following criteria: (1) The local coherence (LC), which is a measure of the variation of the phase in a certain neighborhood, is above a given threshold at the location (i, j), (2) the variability of the predictions /pi;j;i0 ;j0 is below a given threshold, and (3) the difference between the common prediction /pi;j and the unwrapped phase /ui;j is within a certain limit. During unwrapping all thresholds are relaxed step by step. This ensures that pixels for which reliable predictions can be made easily are unwrapped first. Unwrapping can be done in several regions at the same time. If regions overlap and their predictions are in good agreement, they are merged. If their predictions disagree, the pixels in the overlap area are removed from both regions in the hope that the two regions will overlap later on with better agreement. As soon as two regions have been merged, a seed point for a new region is chosen. 2.3. Defining quality measures Local coherence, which was proposed for seed finding and guiding unwrapping in the original algorithm, is a measure of the variation of the phase. It is low in areas with steep phase topography and in the presence of pure noise. Unfortunately, in MR imaging, situations exist in which the signal has a very small magnitude, but the phase is rather coherent. An example of such a situation are ghosting artifacts. In such a case, the phase can be very coherent even in areas where the signal’s magnitude is diminishing (Fig. 1c). Thus, by using local coherence as a quality criterion, the algorithm tries to unwrap areas with low signal but coherent phase before it grows into regions with high signal but steep phase topography. This can lead to artifacts, since the algorithm may accumulate errors in the low signal regions which then propagate into areas that have a high signal intensity. To find a possible solution to this problem four more quality criteria were defined and evaluated in addition to the local coherence. The five quality maps (an example for each map is given in Fig. 1) are motivated and defined in the following manner: local coherence (QLC) is a measure for the coherence of the phase (Fig. 1c). It is highest if the phase is the same in all pixels within a rectangular area around each pixel. It was intro- 259 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 Fig. 1. Overview of the quality maps for an image with ghosting artifacts. The magnitude and phase of this image are displayed in (a) and (b), respectively. All maps were computed with a rectangular kernel of 5 5 pixels and normalized to [0, 1]. (c) shows the local coherence QLC. The map exhibits the typical properties of QLC: very low values in areas of steep phase topography even if there is significant signal present. Conversely it can have high values in areas where there is almost no signal as long as the phase is coherent. (d) depicts the magnitude of the local average of the complex image QACI. QACI suppresses areas with low signal intensities, and has small values in regions with steep phase topography. The map of the local average of the magnitude QAM is shown in (e). The local variance of the complex image QVCI is given in (f). It separates the object from the background by a dark rim and has low values in areas of steep phase topography. The variance in noisy areas is very low (corresponding to high pixel intensities) even compared to homogeneous areas within the object. This does not favor the variance as a quality criterion because it is lower in noise than in the object. (g) is an example for the local variance of the phase QVPH. It exhibits a behavior similar to QLC. duced in the original algorithm (Xu and Cumming, 1999) and is calculated as Q LC i;j iþdx 1 2 1 X ¼ dx dy dx 1 l¼i 2 dy 1 jþ 2 X dy 1 2 m¼j ^l;m p ; ^l;m j jp ð4Þ where (i, j) are the coordinates of the pixel for which the local coherence is calculated and dx and dy are the dimensions of the kernel. average of the complex image (QACI) reaches its highest values if the phase is coherent and the signal is high (Fig. 1d). Since it takes both magnitude and phase into account it should suppress unwrapping of regions where there is almost no signal present. It is defined as Q ACI i;j iþdx 1 X 1 2 ¼ aACI dx dy dx 1 l¼i 2 X ^ pl;m ; dy 1 m¼j 2 where aACI is a normalization constant ensuring that Q ACI i;j lies within the interval [0, 1]. average of the magnitude (QAM) is a smoothed map of the magnitude image (Fig. 1e). It is normalized such that its values range from 0 to 1. The justification for this approach is that the variance of the phase is inversely proportional to the magnitude (Conturo and Smith, 1990). variance of the complex image (QVCI) measures the variance of the complex image within the surroundings of a pixel (Fig. 1f). It was introduced to allow a better delineation of the object, since the variance is expected to be highest at the borders of the object. By using this measure it should be possible to restrict unwrapping to the object. QVCI is given by 0 Q VCI i;j ¼ d 1 jþ y2 ð5Þ 1 B i;j p i;j @p aVCI 1 dx dy iþdx21 X l¼idx21 jþ dy 1 2 X d 1 m¼j y2 1 ^l;m p ^l;m C p A þ 1; ð6Þ i;j is the local average of the complex image computed with where p a kernel of the same size (dx dy) and aVCI a normalization constant. 260 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 The definition of QVCI ensures that pixels of highest quality (i.e. lowest variance) have a quality of approximately 1. variance of the phase (QVPH) is motivated in the same way as QVCI, but takes only the phase into account (Fig. 1g). It is calculated by ^i;j =jp ^i;j j. ^0i;j ¼ p applying Eq. (6) on the normalized complex image p Each map was computed with kernel sizes of 3 3, 5 5 and 7 7 pixels to study the influence of the kernel size on the performance of the algorithm. for the evaluation (see next section). For this investigation, a seed point that had a quality measure above a certain threshold but differed from the seed point with the highest quality measure (i.e. the seed point that is selected by default) was selected randomly. This procedure was repeated 100 times for each slice. Each result was compared to the unwrapped phase obtained with the seed point selected by the algorithm. This was repeated for two different thresholds (0.95 and 0.99). 3.2. Evaluation of UUN 2.4. Seed finding Since the placement of seed points is of utmost importance for the reliability of the prediction of the unwrapped phase, we separated seed finding from the actual unwrapping. It is thus possible to use different quality measures for seed finding and for unwrapping. We have studied the suitability of all maps defined in the previous section for seed finding. All maps were calculated with kernel sizes of 5 5 as well as with 15 15. The reason for using larger kernels is that the resulting map represents a more global quality measure than the one computed with a smaller kernel. While unwrapping requires a rather local quality measure to avoid premature termination, seed finding should profit from a large scale quality measure. Since searching for the ‘‘best” seed point (i.e. the seed point having the highest quality measure) is rather expensive if it has to be repeated, we used the following approach: before unwrapping starts the program creates a list of all possible seed points. This is done by adding all pixels having a quality measure above a threshold to a list. For performance reasons the seed points are not sorted, but divided into small groups having approximately the same quality. In each group, only the seed points having the highest quality are sorted (we also investigated the robustness of the algorithm with respect to the exact location of the seed point. This is described in a later section). Every time a new seed is needed (i.e. just before unwrapping starts and after two regions have been merged) a seed point is taken from the top of the list. A check whether this seed point or its neighborhood have been unwrapped is then performed. If this is the case it is not selected and removed from the list of possible seed points and a new seed point is selected. This procedure avoids the expensive task of merging for newly created regions. 3. Methods 3.1. Implementation and optimization of the method The unwrapping algorithm was implemented in C. UUN has a command-line interface (i.e. stand-alone program) and an interface that allows for an seamless integration into IDL (ITT Visual Information Solutions, USA) and Matlab (Mathworks, USA). Two variants of the algorithm were implemented in the same program: one in which only a single region is used for unwrapping and one in which multiple regions grow simultaneously. The first was motivated by a desire for the highest possible processing speed, the latter by the need to unwrap poorly connected areas. The influence of the quality maps was studied on brain data-sets acquired on a 1.5 T system (Magnetom Vision, Siemens Medical Solutions, Germany) and on a 3 T scanner (Medspec Avance, Bruker Medical, Germany). All data were acquired with the standard quadrature transmit/receive head coil of each system. From this study a set of default parameters was defined. This set of default parameters was then used for the evaluation of UUN’s performance. In addition, we studied the stability of UUN with respect to the location of the seed point on one of the subject data-sets acquired To evaluate the performance of UUN we compared its performance in terms of quality of the unwrapped phase images as well as the required computation time with PRELUDE which is a well established method for unwrapping MRI data-sets. PRELUDE is part of the FSL Analysis Package (Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, United Kingdom). PRELUDE falls into the class of algorithms commonly known as ‘‘Split and Merge” algorithms. Unlike UUN, PRELUDE allows for unwrapping to proceed not only in two, but also in three dimensions. Depending on command-line parameters, the unwrapping proceeds in two dimensions, three dimensions or in a hybrid mode. In the latter, the regions are labeled (the labeling corresponds to the split phase) in two dimensions while the unwrapping itself is done in three dimensions. According to the manual, this is the default mode for high-resolution data-sets. In the case of our data, PRELUDE treated data-sets with dimensions of 256 224 12 (voxel size: 1 1 2 mm3) as high-resolution data-sets. Both programs were applied to the data using their default parameters. The only exception were the parameters controlling the various modes (single region and multiple regions in case of UUN, and default (hybrid) mode, 2D mode, and 3D mode in case of PRELUDE). All data-sets were unwrapped on a multi-processor Linux machine consisting of two dual-core AMD Opteron processors running at 2 GHz. It was ensured that one processor was only used for unwrapping. At all times the machine had a sufficient amount of free memory to guarantee that computation times were not influenced by swapping. Prior to unwrapping the data were copied onto the machine’s local disk to ensure fast and reproducible data access. The amount of time required to load a full complex valued data-set and to write back a floating point data-set was measured and found to be negligible (6.2 103 s for a 256 224 slice). The results of UUN and PRELUDE in all modes were compared with respect to the time required for unwrapping, the agreement of the unwrapped phase images and, in case of disagreements, the plausibility of the unwrapped phase. Differences between the unwrapped phase images were identified by subtracting the phase images from each other. A multiple of 2p was subtracted from the subtraction image if there was an offset between the images. Pixels in which the phase difference differed from 0 were then investigated in the magnitude image, the wrapped phase image and the unwrapped phase images to obtain an understanding for the reasons of the different results. 3.2.1. Phantom data The phantom consisted of a 5 L glass bowl with a ping-pong ball immersed in an aqueous solution containing 0.9% NaCl and 0.2 mmol/l Gd-DTPA. A total number of 72 fully flow compensated 3D gradient echo (Reichenbach and Haacke, 2001) data-sets were acquired on a 1.5 T system (Magnetom Vision, Siemens, Erlangen, Germany) using different echo times, flip angles and resolutions. Of those 72 scans, 48 were low resolution scans (FoV: 256 224 96 mm3, Matrix: 256 168 48; i.e. having a voxel S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 dimension of 1 1.33 2 mm3). The echo time TE and flip angle a of each scan represented a point in the parameter space TE a with TE 2 {20, 25, 30, 35, 40, 45} ms and a 2 {2, 4, 6, 8, 10, 15, 20, 25}°. Every combination of TE and a was utilized. The FoV was placed such that the whole ping-pong ball and a substantial amount of the aqueous solution were covered. Both the magnitude and the phase of a sagittal and a transverse cut through the phantom can be seen in Fig. 2. Of the other 24 data-sets 12 were low resolution scans (FoV: 256 224 48 mm3 Matrix: 256 168 32; i.e. voxel Fig. 2. A sagittal slice of the phantom (magnitude: (a), wrapped phase: (b)) and a transversal slice of the phantom (magnitude: (c), wrapped phase: (d)). The arrow heads in (a) indicate the slices in which the ROIs for calculating the SNR were placed. 261 dimension: 1 1.33 1.5 mm3). The other 12 were high-resolution scans (FoV: 256 224 48 mm3, Matrix: 512 336 32; i.e. having a voxel dimension of 0.5 0.67 1.5 mm3). The parameter space TE a was spanned by TE 2 {20, 30, 45} ms and a 2 {2, 4, 8, 16}°. Again, each low resolution and each high-resolution scan represented one of the possible combinations of TE and a. For these data-sets the FoV did not cover the full ping-pong ball. The repetition time TR was 60 ms for all scans. Before reconstruction, the data were zero-filled such that the in-plane resolution was 1 1 mm2 and 0.5 0.5 mm2, respectively. We ensured that the echo was centered in the z direction. This minimized the number of wraps in z direction. This was done to avoid penalizing the three dimensional methods. In the in-plane phase encoding direction, the echo was shifted from the center to obtain a more complex phase topography. After reconstruction, the outermost slices were discarded, because they did not only contain little signal, but also wrap arounds. For comparing the performance on data-sets with a complex and a simple phase topography we separated each data-set into two sub-sets one having a rather homogeneous (13 slices) and one containing inhomogeneous (20 slices) magnetic field. The homogeneous sub-set did not exhibit significant distortions caused by the field inhomogeneity. In total, 216 data-sets were created. Additionally, we studied the dependency of UUN’s and PRELUDE’s (in 2D mode) performance on the number of wraps on two neighboring slices from three low resolution sets (SNR = 5.1, 14.9 and 83.0, respectively). The slices were chosen such that they were still affected by the field inhomogeneity but had sufficient SNR to be completely unwrapped by all methods. Each slice was reconstructed several times. For each reconstruction the echo was shifted in phase encoding direction by a different Fig. 3. A typical magnitude (a) and phase (b) image of a data-set that suffered from strong field inhomogeneities in the frontal areas caused by the paranasal sinuses (denoted by the white rectangle). The image was unwrapped by UUN using QLC, QACI and QAM to guide the unwrapping procedure. The termination criteria were optimized for each map in such a way that the unwrapping proceeded as far as possible but was limited to the object. The results are shown in the bottom row. By using QLC (c) the algorithm fails to unwrap the frontal areas. Although, QACI (d) leads to an improved unwrapping of those regions, the best results are obtained with QAM (e). 262 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 amount. The maximum displacement of the echo was 33 voxels. The number of phase wraps in the resulting images ranged from 6 to 31 depending on how far the echo was shifted off center. The median distance between wraps ranged from 22.0 to 6.5 voxels, respectively. Each data-set was unwrapped with the methods described above. For each data-set the SNR was estimated for a homogeneous region and for a region that was still subject to the field inhomogeneities caused by the ping-pong ball. 3.2.2. Data of human subjects Data of five healthy subjects acquired with the same sequence as above on the same 1.5 T system (Magnetom Vision, Siemens, Erlangen, Germany) were investigated retrospectively. The parameters were TR = 65 ms, TE = 40 ms, a = 25°, field of view (FoV) 25.6 cm 19.2 cm 6.4 cm, matrix size 512 256 32, acquisition time 10 min, imaging volume parallel to the AC–PC line. The data were zero-filled before reconstruction to achieve isotropic in-plane voxel dimensions. All data were unwrapped with UUN in both single and multiple region mode and PRELUDE in all three modes. The results were analyzed in the same manner as the phantom data. 4. Results 4.1. Definition of default parameters Since the extent to which the algorithm unwraps the phase within the object is controlled by the applied quality map and a respective threshold, the question of interest was which quality map allowed for defining a threshold that was applicable to all data-sets. The performance was evaluated in terms of wrongly unwrapped pixels within the object and how well the algorithm would unwrap areas of steep phase topography. Local variance of the complex image QVCI provided a delineation of the object by a rim of pixels with small intensities. Nevertheless, this measure turned out to be of limited use for two reasons: firstly, the variance was higher in the object than in areas containing noise only. Secondly, it was not possible to define general thresholds because of the large range of values within the maps. Applying a transformation such as logarithmic scaling instead of the normalization did not improve the situation. The local variance of the phase QVPH exhibited the same properties as the local coherence QLC, namely very low values in areas that had sufficient signal but a steep phase topography while it had rather high values in areas with no significant signal but coherent phase due to ghosting artifacts. The expected improvement of the delineation of the object did not occur. The local average of the complex image QACI also did not lead to an improvement compared to the local coherence QLC, because variations of the phase within a pixel’s surrounding had a larger influence on its values than the intensity. Fig. 3 shows the unwrapped phase images obtained with QACI and QAM which were found to be most suitable as quality measures compared to QLC. Both, QACI and QAM led to a significantly better unwrapped phase image in areas of steep phase topography (Fig. 3d and Fig. 3e, respectively). Nevertheless, the algorithm consistently grew farther into regions with large phase gradients and unwrapped more pixels with QAM than with QACI. In areas where using all three quality measures resulted in an unwrapped phase, no difference in the phase images was observed. In conclusion we found that unwrapping performed best with local average of magnitude QAM calculated with a kernel size of 5 5 pixels. However, using QAM for seed finding produced considerable artifacts in some cases, as it placed seeds into areas that had a high signal but were poorly connected to the bulk of the object. Thus the algorithm had to grow along paths with low quality pixels before unwrapping the rest of the brain. This allowed errors to accumulate and propagate into the bulk of the signal containing areas. Fig. 4b displays an image that was affected by such an artifact. The correctly unwrapped phase image is shown in Fig. 4c. For the latter, QLC was used for seed finding. Using QLC computed with a comparatively large kernel (15 15) led to the most reliable placement of seed points. By using QLC, UUN was very robust with respect to the exact location of the seed point. Phase images unwrapped using seed points placed randomly in areas that had a quality measure higher than 0.99 and 0.95, respectively, did not show significant differences. Depending on the phase topography of the slice, the area from which a seed point was chosen randomly encompassed between 7% and 42% of the pixels that were unwrapped in case of QLC > 0.99 and between 45% and 81% for QLC > 0.95. For the higher threshold, disagreements were observed for three of the 64 slices. However, not more than 6 pixels at the rim of the brain were affected. In case of the lower threshold, the number of slices in which disagreements occurred increased to ten. Also in this case, the number of affected pixels did not exceed six. All affected pixels were at the boundary of high SNR areas. In conclusion we found that the use of QLC computed with a large kernel (15 15) produced the most robust seed points (i.e. seed points which led to reliable unwrapped phase images). Fig. 4. Example of an artifact caused by seed points that were placed into a region poorly connected to the rest of the brain. (a) shows the magnitude image, (b) the unwrapped phase image that is affected by an artifact because unwrapping started in the sagittal sinus, (c) correctly unwrapped phase image. In case of (b) the local average of magnitude QAM was used for seed finding. (c) was obtained by applying local coherence QLC to seed finding. The arrow heads indicate the areas where seeds were placed. S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 Unwrapping time normalized [s/#slices] 0.6 4.2. Evaluation of UUN’s performance on phantom data PhUN (default parameters) PhUN (multiple regions, n=100) Prelude 2D Prelude 3D Prelude (default parameters) 0.55 0.5 All data-sets were split into two parts. The first slab contained the ping-pong ball causing the susceptibility difference and was thus strongly affected by the field inhomogeneity. These data were used to investigate the dependency of all methods on computational complexity and SNR. The signal intensity in the second slab was more homogeneous. The performance with respect to resolution, SNR and phase wrap density was investigated on these data. 0.45 0.4 0.35 0.3 0.25 0.2 0.15 0.1 10 20 30 40 50 60 70 80 90 SNR Fig. 5. Time required for unwrapping the ‘‘homogeneous” slab of the low resolution data-sets measured with TE = 25 ms normalized to a single slice. Normalized unwrapping time [s/#slices] 3.5 PhUN (SNR= 5.1) PhUN (SNR=14.9) PhUN (SNR=83.0) PRELUDE 2D (SNR= 5.1) PRELUDE 2D (SNR=14.9) PRELUDE 2D (SNR=83.0) 3 2.5 263 4.2.1. Dependency on spatial resolution UUN and PRELUDE unwrapped both the low and the highresolution data-sets. All differences observed between the performance on the low resolution and high-resolution data-sets could be attributed to the significantly lower ( a factor 4) SNR of the high-resolution data-sets and are thus described in the next section. The time required by UUN for unwrapping was almost independent of SNR and scaled linearly with the fourfold number of voxels (0.51 s/slice compared to 0.14 s/slice for single region mode and 0.84 s/slice versus 0.20 s/slice in multi-region mode). PRELUDE in 2 D mode had a similar increase in computation time (0.5 s/slice vs. 0.14 s/slice) for the high-resolution data-set with the highest SNR. The increase in computation time for PRELUDE’s 3D and hybrid modes was slightly lower. 2 1.5 1 0.5 0 0 5 10 15 20 25 30 35 # wraps Fig. 6. Dependency of UUN’s and PRELUDE’s (in 2D mode) performance on the number of wraps in a slice at different SNR levels. The number of wraps was modulated by shifting the echo off center before reconstruction. While UUN’s speed is independent of the number of wraps and SNR, the time required by PRELUDE increases with increasing number of wraps and decreasing SNR. 4.2.2. SNR dependency The SNR of the low resolution data-sets ranged from 15.4 to 90.6. Even lower SNR (3.7–22.1) was measured in the high-resolution data-sets. Above an SNR of 13 the results of all methods were in perfect agreement. The unwrapped phases were smooth and all pixels within the phantom were unwrapped. Compared to PRELUDE, UUN tended to unwrap an additional one pixel wide rim at the border of the phantom. This behavior was caused by slightly different termination conditions. Below an SNR of 13, UUN still yielded smooth and fully unwrapped phase images. PRELUDE failed to unwrap an increasing number of pixels with decreasing SNR. These pixels were not connected and appeared like salt and pepper noise. The Fig. 7. Illustration of the influence of measuring parameters and echo shifts on the phantom data. The top row displays data that were acquired with TE = 20 ms and a flip angle of a = 25°. The SNR was calculated to be 80.3 in the center of the image. (a) is the magnitude image, (b) the phase image with the echo centered and (c) the phase image with the echo shifted to achieve the maximum number of phase wraps. The bottom row exhibits data of the same phantom acquired at TE = 45 ms and a = 2°. (d) shows the respective magnitude image. The SNR in the center of the image is 5.1, (e) and (f) are the phase images with the centered and the maximally off-centered echo, respectively. 264 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 a b c e d f 35 Wrapped phase PhUN PRELUDE 2D phase wrap 30 25 20 Phase 15 10 5 0 0 50 100 150 200 250 x Fig. 8. A slice of the phantom ((a) magnitude image, (b) phase image) unwrapped by UUN (c) and PRELUDE 2D (d). (e) shows the difference between the results obtained with UUN and PRELUDE. White pixels indicate pixels for which UUN computed an unwrapped phase but not PRELUDE, black pixels those which were unwrapped by PRELUDE but not by UUN. In (f) the phase along a cut parallel to the x-axis at the center of the slice is shown. At about pixel 150, PRELUDE generates an artificial phase wrap. This wrap is indicated in (d) and (e) by the arrow heads. It is hardly visible because of its small size and the rather large dynamic range of the image (the lowest value is 51.79, the highest 42.46). 4.2.3. Sensitivity to phase wrap density The number of phase wraps was modulated systematically by shifting the echo from the k-space center in phase encoding direction. In total, 20 data-sets with 6–31 phase wraps were generated. This corresponded to a median distance between wraps of 22.0 and 6.5 voxels, respectively. Both UUN and PRELUDE (in 2D Normalized unwrapping time [s/#slices] number of those pixels increased from a single pixel in single slices at SNR 13 to 1.5% of the object at the lowest SNR (SNR 3.7). Below an SNR of 8, PRELUDE in 3D and hybrid (default) mode failed to unwrap the data within 24 h and was terminated manually. At these low SNR levels, PRELUDE in 2D mode also tried to unwrap the area outside the phantom. This led to a sharp increase of time required for unwrapping (a factor 10 at SNR 7 and more than a factor 1000 at SNR < 4, respectively). At SNR levels below 4, UUN also started unwrapping the area outside of the phantom. This led to a 10 times slower unwrapping. UUN’s computation time was independent of SNR, except for the data-sets with SNR < 4. UUN required 0.14 s for unwrapping a low resolution slice in single region mode and 0.2 s in multi region mode. At high SNR, PRELUDE even was slightly faster 0.12 s/slice in 2D and 3D mode. At SNR levels below 50, the time required by PRELUDE exhibited a strong dependence on SNR. This is especially obvious in the 3D and the default (hybrid) mode. Fig. 5 shows the computation times normalized to a single slice for a slab of the low resolution data measured with TE = 25 ms. For longer TE this behavior was even more pronounced, because the number of phase wraps increased with longer TE. For TE = 45 ms, PRELUDE required 0.12 s/slice at the highest SNR and 0.15 s/slice at SNR 15 in 2D mode, between 0.14 s/slice and 0.37 s/slice in 3D mode and between 0.24 s/slice and 0.81 s/slice in hybrid mode. 100 PhUN (default parameters) PhUN (multiple regions, n=100) PRELUDE 2D PRELUDE 3D PRELUDE (default parameters) 10 1 0.1 0 10 20 30 40 50 60 70 80 90 SNR Fig. 9. Time required for unwrapping data-sets containing the source of the field inhomogeneity normalized to a single slice (on a logarithmic scale) versus the SNR measured in a ROI affected by the field inhomogeneity. The SNR in this ROI serves as an estimate for the complexity of the unwrapping problem. S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 mode) unwrapped all images. All unwrapped phase images were perfectly smooth and in exact agreement (except for the one pixel wide rim around the phantom described above). The time required to unwrap a slice was comparable up to 17 wraps contained within the object (corresponding to a median distance between wraps of 12 voxels). Up to this wrap density, both methods needed less than 200 ms for each slice at all SNR levels and the time was approximately independent of the number of wraps (see Fig. 6). While UUN’s unwrapping speed did not show any change at higher wrap densities, PRELUDE’s unwrapping time exhibited a strong dependency on both number of wraps in the object and SNR (the SNR was calculated for the center of the image which was most strongly affected by the field inhomogeneity). For high SNR images (SNR = 83.0) unwrapping the images with the largest number of wraps (31) took PRELUDE approximately 5 times as long as unwrapping the images with up to 17 wraps. In case of the low SNR images (SNR = 5.1), PRELUDE’s unwrapping was about a factor 20 slower than UUN. Fig. 7 displays the effects of both measuring parameters and shifting of the echo. 4.2.4. Computational complexity Since the phase topography around the ping-pong ball was complex, the dependence of the performance on the computational complexity was investigated on the slab containing the ping-pong ball. The SNR measured in the ROI in proximity to the ping-pong ball varied with TE and flip angle and provided a measure for the complexity of the unwrapping problem. The SNR ranged from 5.1 to 84.3 for the low resolution data. 265 The results of all modes of UUN and PRELUDE were in very good agreement for all SNR levels. The only differences were: In the areas most strongly affected by the field inhomogeneity (SNR 3), PRELUDE unwrapped further into the region affected by the signal drop-out, but left small ‘‘holes” of wrapped pixels. UUN, on the other hand, created a smoother phase topography, in some small areas (well below 100 pixels in size) with very steep phase topography, PRELUDE created phase wraps and the results of the different modes were not consistent. The phase images computed by UUN did not show these wraps. A slice that exhibits these discrepancies is shown in Fig. 8. The computation time of UUN remained constant with increasing computational complexity (i.e. decreasing SNR and increasing number of phase wraps). UUN required 0.15 s/slice in single region mode and 0.2 s/slice in multi-region mode. PRELUDE’s run-time, however, exhibited a strong dependency on computational complexity. In 2D mode, PRELUDE had a performance comparable to UUN (0.26 s/slice) in case of the data with the lowest complexity (i.e. corresponding to the highest SNR in the region affected by the field inhomogeneity). At the lowest SNR, the time required increased by a factor 2.5. In case of the high SNR data, PRELUDE in 3D and hybrid mode was more than a factor 14 slower (2.1 s/slice and 5.15 s/slice). The computation time for those two modes increased up to 7.38 s/slice and 19.2 s/slice, respectively. Compared to UUN, this corresponds to an unwrapping time increased by a factor between 50 and 130. Fig. 9 displays the computation time behavior of UUN and PRELUDE. Fig. 10. A single slice of one of the subjects ((a) magnitude image, (b) phase image) unwrapped by UUN (c) and PRELUDE 2D (d). (e) shows the difference between the results obtained with UUN and PRELUDE. White pixels indicate pixels for which UUN computed an unwrapped phase but not PRELUDE, black pixels those for which PRELUDE calculated an unwrapped phase but not UUN. Except for the fatty area around the brain, of which UUN unwrapped only a small fraction, there are small differences in the frontal area because of different termination criteria. Within the brain there are four pixels that were not unwrapped by PRELUDE. 266 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 4.3. Performance on subject data The results of UUN, both in single region as well as in multiregion mode, and PRELUDE in 2D and in hybrid (default) mode were in very good agreement; within the brain, at maximum single pixels per slice differed. In those situations, even close inspection did not reveal which prediction was more likely than the other. In most cases, the reason for the disagreements was that the pixels had very low magnitude. In other cases, it was single pixels surrounded by pixels with very low magnitude. Just as in the phantom, PRELUDE tended to grow slightly further into areas where the signal was very low (Fig. 10). Although in general, PRELUDE in 3D mode was in good agreement with the other methods, it occasionally created wraps in places where there were none before unwrapping (Fig. 11). In all cases, UUN in default mode outpaced all other methods in terms of speed. UUN needed just below 0.4 s for unwrapping a single 384 512 slice. In multi-region mode UUN required between 0.6 s and 0.8 s. Unwrapping a slice with PRELUDE in 2D mode took between 2.49 s and 7.59 s per slice. The computation time for each slice ranged from 29.42 s to 397.56 s for PRELUDE in 3D mode and for PRELUDE in default (hybrid) mode from 383.16 s to 1509.13 s (Fig. 12). 5. Discussion 5.1. Algorithm We proposed a region growing phase unwrapping method that exploits magnitude information for guiding the unwrapping and phase information for selecting seed points. Since region growing algorithms depend on the criteria used for growing the region and placing seed points, we believe that the choice of the quality map is crucial as it should reflect the phase image’s underlying physics and take into account the characteristics of the method for estimating the unwrapped phase. There is an important difference between using magnitude information for guiding the growth of regions compared to simply using it as a termination criterion in the form of a mask. The quality map can be rather seen as a dynamic mask that is adjusted to the Fig. 11. Wrapped phase (a) of a subject where PRELUDE in 3D mode generated phase wraps that were not present in the original phase image (b). For comparison the phase image obtained with UUN is shown in (c). The position of the artifact produced by PRELUDE is indicated by arrow heads in all three images. Normalized unwrapping time [s/#slices] 1,000 100 10 1 0 Φ UN (default parameters) Φ UN (multiple regions, n=100) PRELUDE (default parameters) PRELUDE 2D PRELUDE 3D Fig. 12. Comparison of the time required for unwrapping SWI data-sets of five different subjects. For better comparison the times were normalized to a single slice. While UUN achieved unwrapping times below 400 ms in single region mode and less than 800 ms in multi-region mode, PRELUDE was about 10 times slower in 2D mode. Furthermore, PRELUDE used with default parameters and PRELUDE in 3D mode were between 100 and 5000 times slower than the 2D Region Growing Phase Unwrapping program. S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 unwrapping stage. The argument that magnitude information should be incorporated in guiding the unwrapping can even be made without considering that the magnitude is related to phase SNR. Information of pixels with significant signal strength is more reliable than of those without. Nevertheless, since a linear prediction is used to estimate the phase, a flat phase topography is preferable at early stages of a region’s growth process. Since this cannot be ensured by using magnitude information, we incorporate phase information for seed finding by using local coherence (QLC). If the seed points are placed into areas of flat phase topography the algorithm is very robust with respect to the location of the seed point. This was shown by randomly selecting seed points. If seed points were also set in areas with lower QLC the number of phase images with disagreements increased. This shows that although the exact location of the seed point is not of great importance the phase topography around the seed point has to be reasonably flat. As any post-processing step, UUN has certain constraints and requirements on the data it is applied to. The complex images have to be acquired in a way that the phase information is not distorted. Although this might seem obvious, it is often not the case. The most common reasons for distorted phase images are: (1) Incorrectly combined data obtained with phased array coils can introduce singularities to the phase image. These singularities are often referred to as open-ended fringe lines (Chavez et al., 2002). In such situations it is not possible to describe the phase by a continuous function. The issue of combining data of the coil elements of a phased array coil is a very complex one. Its discussion is beyond the scope of this publication. For a thorough discussion of the theoretical basics we refer the reader to (Roemer et al., 1990). (2) Filters that are applied to the data may cause singularities in phase images. Especially noteworthy is homodyne detection. In general, it is not possible to remove phase wraps that remain after homodyne detection by applying phase unwrapping, since these phase images usually contain singularities. (3) Images which were scaled or rotated by operations that were applied to the phase and magnitude images separately. As a result the sharp edges that characterize phase wraps can be smeared out and thus not appear as a phase wrap. If image scaling or rotation are to be performed prior to unwrapping they have to be either done in fourier space (i.e. by zero filling in case of scaling) or on the real and imaginary part of the complex image. In images in which the phase information is not distorted by either a filter or incorrectly combined phase images, open ended fringe lines appear only in areas with very low SNR. Since the algorithm does not grow into those areas if magnitude information is used for guiding the unwrapping, UUN does not attempt to unwrap open ended fringe lines. UUN does not make any assumptions on the orientation in which the data was acquired. While the orientation of a slice can have an impact on the phase image itself (especially if the voxels are anisotropic), the problem of phase unwrapping is not changed. UUN has successfully unwrapped data acquired in sagittal orientation (Koopmans et al., 2008), for instance. However, since phase predictions of all prediction lines are regarded in the same manner for computing a common prediction, isotropic in-plane voxel dimensions are assumed implicitly. If the voxel dimensions are very anisotropic it might be necessary to account for this anisotropy by using weights depending on the direction of the prediction line. 267 MRI data can be volume data in which there is no gap between slices. One could assume that a three dimensional approach would provide a better performance than unwrapping slice by slice. The performance of PRELUDE in 3D and hybrid mode show that this is not necessarily the case. The artifacts produced by PRELUDE in 3D mode are another indication that three dimensional phase unwrapping does not necessarily lead to a better unwrapping. In many cases, fully three dimensional unwrapping is not necessary. As long as each slice has been unwrapped reliably, adding multiples of 2p removes inconsistencies across slices. Furthermore, for example in SWI, an important three dimensional application, only high frequency phase variations are of interest. Thus, because the phase images are corrected for low frequency phase variations, any inconsistency across slices is removed. In principle, extending the algorithm to three dimensions is straightforward. Nevertheless, we were reluctant to modify our approach mainly because of the following reasons. Firstly, in three dimensions each voxel has 26 instead of eight neighbors. This increases not only the number of predictions that have to be calculated for each voxel, but also the chances that the common prediction fails to meet the criteria for being unwrapped. This would increase the computation time significantly, which is contrary to the aim of our implementation (namely to provide fast unwrapping). Secondly, in many cases, the slice thickness is much larger than the in-plane voxel dimensions. This anisotropy would have to be taken into account. This would add additional complexity and parameters to the problem. 5.2. Evaluation and comparison We based our evaluation and comparison entirely on measured and not on simulated data. In measured data the true phase cannot be known. On the other hand, phase and magnitude images are mutually entangled, and a simulation would have to take both properties into account, without losing information on the absolute phase. Furthermore, our results show that a comparison between the algorithms’ performances on phantom data and on subject data is very difficult. Simulated data would therefore just give an indication of an algorithm’s performance but would not allow any conclusion about its performance on real data. Because of these reasons and the fact that the results of all methods were in very good agreement in almost all situations, we concluded that knowledge of the ‘‘true” phase was not necessary for our evaluation. The biggest difference between the methods did not lie in the quality of the results but in their speed and its dependency on the complexity of the phase topography and SNR. A closer investigation of the algorithms’ performance on the phantom data showed that, in case of high SNR and low complexity of the phase topography, the times required is approximately the same for all methods and 0.1–0.2 s per slice. However, even for this rather homogeneous data, at lower SNR levels, PRELUDE exhibits an SNR dependency which is largest for the 3D and hybrid algorithm. On the other hand, the times required by UUN are approximately independent of SNR. PRELUDE’s SNR dependency was already described in the original publication (Jenkinson, 2003) where PRELUDE was compared to a minimum spanning tree (MST) algorithm. PRELUDE’s advantage compared to MST was that, while MST had an SNR independent run-time, the number of incorrectly unwrapped pixels increased much faster with decreasing SNR. UUN had fewer incorrectly unwrapped pixels than PRELUDE at extremely low SNR values. Also, while UUN’s performance was approximately independent of the phase topography’s complexity, PRELUDE’s computation time increased with increasing number of phase warps and 268 S. Witoszynskyj et al. / Medical Image Analysis 13 (2009) 257–268 complexity of the phase topography. This behavior was even more pronounced at low SNR and for the 3D and hybrid mode. The salt and pepper noise like artifacts produced by PRELUDE in very low SNR images are caused by the way that PRELUDE uses the magnitude as termination criterion. While UUN bases it’s termination decision on the magnitude averaged over a small area, PRELUDE only considers the magnitude in a single point. At low SNR this results in single pixels that are not unwrapped. This also explains the discrepancies in areas with very low intensity. In those situations, UUN tends to create smoother boundaries, while PRELUDE has a tendency to unwrap further into areas with very low signal. This also causes holes in PRELUDE’s phase images in the same areas. For subsequent processing UUN’s smoother boundary might be advantageous, since small holes correspond to high spatial frequencies. Thus those areas would have to be excluded if a filter is to be applied to the phase image. UUN has been applied only to phantom and brain data so far. An application to other tissues and organs should, in principle, be possible as long as some tissue properties are kept in mind. Brain tissue, for example, does not contain fatty tissue. In case of organs containing fatty tissue the phase within the fatty tissue can be shifted from the phase of the surrounding tissue if the echo time is chosen appropriately. In this situation the phase topography may contain discontinuities or, even worse, singularities caused by partial volume effects. While discontinuities themselves do not pose a problem if unwrapping is done by multiple regions, singularities hamper any phase unwrapping approach. 6. Conclusions We have developed and implemented a fast and robust 2D region growing phase unwrapping algorithm optimized for MRI data. The algorithm’s performance was tested extensively on both phantom and in vivo data and compared to an established method (PRELUDE). Both algorithms performed reliable and similar in high SNR areas, but UUN accomplished unwrapping much faster and more robust in low SNR areas and in case of complex phase topographies. This makes UUN a suitable application for SWI that contain low SNR areas. UUN is freely available for the scientific community. Acknowledgements This study was supported in parts by the European COST action B21 (COST-STSM-B21-00690) and the German Research Foundation (DFG RE 1123/7-2). 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