From: AAAI Technical Report SS-94-05. Compilation copyright © 1994, AAAI (www.aaai.org). All rights reserved. Medical Image Registration using Voxel Similarity Measures tDerek LGHill & David J Hawkes 1. Introduction 1.1. Patients frequently undergomultiple radiological imaging investigationsthat providecomplementary information.It is becomingincreasingly widely recognised that the use of imageprocessing techniques to combinethis information into a single representationof the patient can assist in the interpretation of the relevant radiological information[1]. Thedevelopment of clinically useableautomatic3Dmedical imageregisuation algorithms is therefore an important researcharea. Medicalimagesof the sameregionof a patient acquiredwith different imagingmodalitiesare usually recognisablysimilar, even to a non-expert. For example,MRand CTimages ofmanyparts ofthe bodycontain broadlythe samefeatures, andobserverswhoare newto these types of imageswill frequentlyrecognisethe part of the bodythat has beenimaged, but mistakethe modality. In these visually-similar images fromdifferent modalities, imagefeatures in the different modalitieswill appearwith different intensity andtexture, and someimagefeatures visible in one modality will be absent from another modality. There are important exceptions: projectionangiograms (especially subtractedones)are difficult to relate to cross-sectionalimagesof the samepart of a patient becamethey share almost no imagefeatures due to their different dimensionality;nuclear medicineimages acquiredusingvery specific functionaltracers providelittle anatomicalinformationto relate to other modalities. Cross Correlation of Intensity Values The cross correlation of two functionsis frequentlyused in signal processingand imageprocessingas a measureof how well two functions A and B matchup whenthey are transformedwith respect to each other. ThetransformationT that providesthe best matchbetweenthe functions has the highest con’elationvalue. For two3Dreal valuedimagesAand B with p x q x r voxels, the correlation value for a Wansformation Tis given by equation 1. p-lq-lr-I [A~B]r-- ~, ~_~_Aqt. T(Bii k) (I) i=Oj=Ok=O To determinethe transformationthat most closely matches the twofunctions,it is necessaryto find the valueof T that maximisesthe right hand side of this equation. Thetransformedvalueof Bi]kis unlikelyto lie ona samplepoint in the data, so interpolation is normallyused in the evaluationof T(Bok). Published work in medicalimageregistration using cross correlation of intensity valueshas beenless successfulthan alternative approaches, such as landmarkregistration and surface matching.Tworecently developedtechniques, which are closely related to cross correlation, havebeenmuchmore successful. 1.1.1 Cross Correlation of Image Gradients Wherevisually-similar images are being combined,image Vanden Elsen [7] proposedan algorithmfor imageregistraregistration can be accomplishedby manually,or perhaps tion by correlation of imageintensity gradients. In her algorithm, the secondderivative of the imagein the direction automatically,identifying a small number of equivalentfeatures suchas points or surfacesin the images[2,3,4,5,6]. An normalto the local intensity gradientis usedas a ridge detector. Bychoosingan appropriatescale at whichto calculate alternativeapproach is to performregistrationusingall, or at the derivative, the bone ridge from MRand CTimagescan least a large number of the voxelsin the imagesrather thana be automaticallyextractedfromthe images,and the resulting smallnumberof derivedfeatures. Thebasis of this approach is the assumptionthat somearithmetic combination of voxel gradient imagescan be cross correlated to determinethe correct registration transformation. values in two images,whenappfied to each imagevoxel in turn, provides a similarity measurethat has an optimum 1.1.2 Minimisingthe Coefficient of Variation of Intenvalue whenthe imagesare aligned. The best knownalgosity Ratios rithm of this type is cross correlation. This paper reviews RogerWoods [8,9] has proposedan algorithmthat is related algorithmsusing voxel similarity measuresthat havei~en to cross correlation, but incorporatesan importantmodificaapplied to medical images, and presents new work on a tion. His algorithm is basedon an idealised assumptionthat methodology for devising improvedsimilarity measures. states: if twoimagesare accuratelyaligned, thenthe valueof anyvoxel in one imageis related to the value of the corretRadiologicalSciences,UMDS, Guy’s&St Thomas’ Hospitals, spondingvoxel in the other imageby a multiplicative factor St Thomas"St. LondonSEI 9RT, UK. D.Hill@umds.ac.uk R. In other words,for all voxelsai andbi in imagesAand B Fundedby the UKScienceand EngineeringResearchCouncil. 34 2.2. Qi ~spcctively, ~ = R. WhenA and B am acquired from the ;ame patient using the samemodafityat different times, here will be a single value of R for all intensity values. 0VhenAandB are acquiredfromthe samepatient using dif’erent modalities, there mightbe a different valueof R for ¯ ach intensity value in either image.TheWoods algorithm msbeendevelopedspecifically for registration of multiple ~ETimagesfromthe samepatient, and for registration of ’ETimagesto MRIimagesof the samepatient. Clearly, the dealisedassumption will not holdin either of these applicaions, but, if R is moreuniform(has a lowervariance 2) vhenthe imagesare in registration than whenthe imagesare ,ot, and if 02 increases as the degree of misregistration ncreases, then imageregistration can be accomplishedby ainimisingthe coefficientof variationof the intensityratios. Vehavepreviously shownhowthis techniquecan be modited in order to automaticallyregister MRandCTimagesof ~e head,providedthere is sufficient axial sampling[10]. "he successof these techniquesfor solvingspecific registraon problemsencouragedus to devise a methodologyfor arther investigatingvoxelsimilarity measures. ’,. Similarity measure plots Aquantitative indication of the performance of voxel based registration algorithmscan be gainedby studyingthe wayin whichthe similarity measurechangeswith misregiswafion. Usingregistered referenceimages,the similarity measureis evaluatedfor the imagesat registration, andwhenmisregistered by knowntransformations in each of the degrees of freedomof the desiredregistration transformation.For rigid bodyregistration, this providesa series of six one dimensional curves, eachof whichis a plot of similarity measure valueagainst misregistrationfor a single degreeof freedom. Weterm the resulting graphssimilarity measureplots. The similarity measuresare formulatedas cost functions, so an ideal similarity measureplot has a minimum value at registration, and is a monotonically increasing function of misregistration. It must be emphasisedthat these similarity measureplots do not sampleall of the parameterspace, and there are likely to be manylocal minima (or eventhe global minimum) that are not visible in the similarity measure plots. 2.3. Initial Evaluation of Similarity Measures These techniques have been used to evaluate similarity measureson preregistered MR,CTand PETimages. 3. Results Method Ve have accurately registered manydozens of medical nages using anatomicallandmarks[1]. This provides us ,ith a large number of referencedatasetswith whichto evalate alternative registration algorithms.Wehavedevisedtwo :chniquesfor assessingpossible voxelsimilarity measures: ¯ ,ature spacesequences andsimilarity measure plots. 3.1. Feature Space Sequences ides a wayof studyingthe changein the appearanceof a .ature space with misregistration. Alternative similarity teasures canbe calculateddirectly fromthe feature spaces. A l similar feature space sequence generated from T weightedMRand CTimagesof the skull base is shownin figure2. A feature space generatedfromtwoidentical, perfectly registered images, isa line ofunit gradient. Theappearanceof the feature space changesin a similar waywith misregistralion in eachdegreeof freedomin turn. Thedistinctive diagonal line gradually blurs in the horizontal and vertical directions, Horizontalandvertical lines appear,intersecting .1. Feature Space Sequences at peaksin the original feature space, oncethe misregistra¯ qualitativewayof consideringthe effect of misregistration tion is sufficiently great that a givenintensity valuein one n voxel similarity measures,is to use feature spaces. For imagecan underlie any intensity value in the secondimage. ~e workpresentedhere, feature spacesare constructedfrom Feature space sequenceswere also generatedfor other more nageintensifies. Extendingthis workby generatingfeature relevant imagecombinations.Afeature space sequencewas paces fromimagegradients or texture mightproveuseful. generated from two similar but not identical MRimages. , feature spacesequenceis a series of feature spacescalcu- One MRimagewas generated from the original by adding tted from a pair of imagestransformedrelative to each Gaussiannoise with a standard deviation similar to the standarddeviationof the air in this image,followedby addther. Oneimagein the sequenceis calculated whenthe ing an offset of 100 to each voxel value. The second MR nages arecorrectly registered, theothers arecalculated ’ithknown transformations ina chosen degree offreedom.imagewasgeneratedfromthe sameoriginal by setting the ¯ feature space sequence canbecalculated foreach degree left mostthird of the voxelvaluesto O. Theresulting feature f freedom of the rigid bodytransformation: It thereforepro- spacesequenceis shownin figure 1. 35 These plots demonstrate that the cost increases almost monotonically with misregistrafionin eachof the degrees of freedom.Theequivalentplots obtainedusing cross correlation andthe coeffecientof variation of intensity ratios conrain local minimain each degreeof freedom. le-04 Rgure1. A feature space sequencegenerated fromtwosimilar MRimages registered(a) andtranslatedlaterallyby3ram (b), 9ram (c) and25ram 8e.05 E R~6e-05 0 i 4e-05 ¯ ~,2e-05 O Rgure2. A feature space sequencegenerated fromMRandCTimages registered(a) androtated 2.5"(b), 7.5"(c) and20"(d) abouta cranio-caudal axis. Thet’eature space sequencesshownin ligures 1 and 2, and others gennratedfrom alternative imagecombinations,look quite different. However, there are common characteristics: 1. diagonalfeaturesin the imagesat registration disperse whenthe imagesare misregistered. 2. exceptat the origin, the highestintensitypixels get less bright with misregistration. 3. the number of lowintensity pixels increaseswith misregistration horizontalandvertical lines appearin the feature 4. spaceswhenthe imagesare significantly misregistered. Wedevised a newsimilarity measure,designedto be sensifive to someof the changes in feature space appearance listed above:the third order moment of the intensity histogramof the feature space. Thehistogramof the feature space contains informationaboutthe distribution of feature space intensities. It is weightedtowardshigh values if a small numberof feature space pixels havehigh intensity, and is weightedtowardslow values if a large numberof feature space pixels have low intensity. Thehigher order moments of this histogramquantify its distribution. Wechoseto use the third order moment of the feature space histogram,but the choiceof this rather than anyother moment of order 2 or abovewasarbitrary. Figure3 showsthe similarity measureplots for pre andpost GadoliniumMRimages. These imageswere acquired in the normalclinical routine. The patient wasremoved from the MRscanner for injection of contrast betweenacquisitions, and the voxel dimensionsweredifferent in the two images. 36 o 0°+0030-20 - 10 0 10 20 30 mismgisb’aUon - ~’~slat~n (ram) or m~fion (degrees) Rgure3. A similarity measureplot calculated using the 3rd ordermoment of the feature spacehistogram, for two T1 weightedMRimages(pre and post Gadolinium). Pie and post GadoliniumMRimageshave been successfully registered automaticallywith this similarity measureusing a genetic algorithm[11] with a populationsize of I00 and 30 generations,at twoscales. 4. Discussion In order to register imagesusingequivalentor similar features it is first necessaryto identifythese features. Registration algorithmsof this type require considerableinteraction froma trained operator, becauseautomaticsegmentationand labelling of anatomicalfeatures in medicalimagesremainsa difficult problem.Registration algorithms that use voxel similarity measurespotentially overcomethis difficulty by using imagevoxels rather than derived geometricfeatures for registration. Both RogerWoodsat UCLA and Petra van den Elsen at Utrecht have implementedalgorithms using voxel similarity measuresand successfully registered MR and PET, and MRand CTimages respectively. The former technique requires presegmentationof the brain from the MRimages, and the latter has only beenapplied to images with considerablyhigher resolution than those that are roufinely acquiredclinically. Wehave previously demonstratedthat RogerWoods’algorithm can be extended to the registration of MRand CT images,by modifyingthe algorithmto use only voxel inten- dries within certain ranges. However,the algorithm failed to "egister imageswith insufficient axial sampling. Wehave devised a methodologyfor further evaluation of ~oxel similarity measures,in particular the generationof feame space sequences. All the feature space sequences proluced shared common characteristics that might be used for egistration. The coefficient of variation of intensity ratios algorithm makes one dimensional measurementsin feature :pace: it calculates the coefficient of variation alongthe ordiDate axis. Oneconsequenceof this is that in MRand CTregstration, there is a high cost associated with soft tissue from ¢IR overlying bone from CT, but there is not a correspondng high cost for soft tissue from CToverlying bone from dR. An algorithm that operates on both dimensions of the eamre space might be more reliable. Ye devised an alternative measureof the change in appearnee of the feature space images. This measure, the third ,rder momentof the feature space histogram, was successally used for the automatic registration of MRimages pre nd post injection of Gadolinium.This is an important appliation of image registration, as subtraction of these images an provide useful clinical information [12], and patients ormally movebetween~theacquisition of these sequences. : is an exampleof a large class of imageregistration prob.’ms, in whicha time series of images need to be related. )bvious examples include monitoring disease progression ¯ .g: plaque volumein patients with multiple sclerosis), and orrecting for movement artifacts in functional MR[13]. earching parameter space for the minimumevaluation of a oxel similarity measureis difficult. There can be an enorious numberof local minima. Even if the similarity messre plots suggest that the similarity measure increases mnotonically with misregistration, there can be local dnima, or even a global minimumin an unmeasuredpart of ammeterspace, One reason for this is that the similarity teasures tend to assign a high cost to air overlying tissue. or axial images, misregistration caused by translations in te lateral and posterior-anterior directions, and rotations bout all three axes lead to air overlying tissue. However, tany incorrect transformations will also reduce the amount f air overlying tissue, leading to a local minimum. lore workis neededto devise and test appropriate similarity ~easures, but the approach showsgreat promise of prodnctg an accurate, automatedmethodfor registration of voxel ttasets in 3Dmedical imaging. ¯ References Hill DLG,HawkesDJ, Hussain Z, Green SEM,Ruff CF, Robinson GP. Accurate combination of CT and MRdata of the head:Validation and applications in surgical andther- 37 apy planning. 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Mnltimodality matching of brain Images.Utrecht University Thesis 1993. 8. WoodsRP, Cherry SR, Mazziotta JC. A rapid automated algorithm for accurately aligning and resliceing PET images. J CompAssis Tomogr16:620-633 1992 9. WoodsRP, Mazziotta JC, Cherry SR. MRI-PETregistration with automated algorithm. J CompAssis Tomogr17: 536346 1993 10. Hill DLG,HawkesDJ, Harrison N, Ruff CF. A strategy for automatedmultimodality registration incorporating anatomical knowledgeand imagercharacteristics. In: Barrett HH,Gmitro AF, eds. Information Processing in Medical ImagingIPMI’93. Lecture Notes in ComputerScience 687 Springer-Verlag,Berlin. pp 182-196.1993 11. GoldbergDE. Genetic algorithms in search optimisation and machinelearning. AddisonWesley, Mass. USA.1989 12.Lloyd GAS,Barker PG, Phelps PD. Subtraction gadolinium enhancedmagnetic resonance for head and neck imaging. 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