Current Technological Advances in Magnetic Resonance With...

Current Technological Advances in Magnetic Resonance WithCritical Impact for Clinical Diagnosis and Therapy

Val M. Runge, MD

Abstract: The last 5 years of technological advances with major impact onclinical magnetic resonance (MR) are discussed, with greater emphasis on thosethat are most recent. These developments have already had a critical positiveeffect on clinical diagnosis and therapy and presage continued rapid improve-ments for the next 5 years. This review begins with a discussion of 2 topics thatencompass the breadth of MR, in terms of anatomic applications, contrast media,and MR angiography. Subsequently, innovations are discussed by anatomic cat-egory, picking the areas with the greatest development, starting with the brain,moving forward to the liver and kidney, and concluding with the musculoskeletalsystem, breast, and prostate. Two final topics are then considered, which willlikely, with time, become independent major fields in their own right, interven-tional MR and MR positron emission tomography (PET).

The next decade will bring a new generation of MR contrast media, withresearch focused on substantial improvements (9100-fold) in relaxivity (contrasteffect), thus providing greater efficacy, safety, and tissue targeting. Magneticresonance angiographywill seemajor advances because of the use of compressedsensing, in terms of spatial and temporal resolution, with movement away fromnondynamic imaging. The breadth of available techniques and tissue contrast hasgreatly expanded in brain imaging, benefiting both from the introduction of newbasic categories of imaging techniques, such as readout-segmented echo planarimaging and 3D fast spin echo imaging with variable flip angles, and from newrefinements specific to anatomic areas, such as double inversion recovery andMP2RAGE. Liver imaging has benefited from the development of techniquesto easily and rapidly assess lipid, and will see, overall, a marked improvementin the next 5 years from new techniques on the verge of clinical introduction,such as controlled aliasing in parallel imaging results in higher acceleration(CAIPIRINHA), with a substantial impact on both spatial resolution and scan time.Renal MR is benefiting from the application of blood-oxygen-levelYdependentimaging, providing an assessment of renal function critical for the evaluation ofchronic kidney disease. Techniques to reduce metal artifact are a major focus ofdevelopment in musculoskeletal MR and are critical for the ever-increasingpostsurgical and implant patient population, leading to markedly improved im-aging of tissue adjacent to metal and diagnosis of infection, prosthesis loosening,and postsurgical complications such as fracture. In breast MR, scan techniquesare continuing to evolve, and the impact of this examination on screening for andevaluation and treatment of breast carcinoma is substantial with continued ex-pansion of indications. Prostate MR has benefited frommultiparametric imagingand the application of diffusion-weighted imaging, the latter technique also nowapplied more generally in body imaging, with a substantial clinical impact, inparticular for the detection of tumor lymph nodes. Interventional MR is still earlyin its development, although well established in many centers, possessing greatpotential in comparison with computed tomography (CT) because of superiorsoft-tissue contrast, real-time multiplanar imaging guidance and monitoring, theavailability of temperature mapping, and the lack of ionizing radiation. And lastbut not least, MR-PET is in its infancy, with the first round of clinical unitsinstalled in the past 2 years and early clinical experience showing equivalenceand, in some instances, superiority to PET-CT. As with the field of MR itself,

which began when CTwas already an established modality, MR-PETwill likely,in the next decade, become an equivalent modality to PET-CT, if not begin tosupplant the latter modality.

Key Words: magnetic resonance, MR, magnetic resonance imaging, MRI,magnetic resonance angiography, MRA, contrast-enhanced MR angiography,contrast media, gadolinium chelate, brain, liver, neoplastic disease, kidney,musculoskeletal system, imaging, tumor diagnosis, breast, breast carcinoma,prostate, prostate carcinoma, interventional MR, RF ablation, cryoablation,laser ablation, MR-guided focused ultrasound, MR-guided biopsy, MR-PET,PET/MR, PET

(Invest Radiol 2013;48: 869Y877)

This review draws primarily upon research published in Investi-gative Radiology during the past 5 years, with reference, on oc-

casion, to relevant work published elsewhere in the literature. Hottopics are emphasized by reference to abstracts presented at the mostrecent International Society for Magnetic Resonance in Medicinemeeting, held in late April 2013 in Salt Lake City, UT. Focusing on thetopics most widely applicable today and in the immediate future fordepartments of diagnostic radiology worldwide, research involving theheart and studies conducted at 7 Twere intentionally excluded.

Contrast MediaThe injection of intravenous contrast media, specifically the

use of gadolinium chelates, is an integral part of clinical magneticresonance (MR) today. Almost half of administered doses are for theevaluation of central nervous system disease, with additional majorareas being contrast-enhanced MR angiography (CE-MRA), liverimaging, and breast evaluation for malignancy.

Targeted MR contrast agents are in their infancy. Seminalwork in the last 5 years examined a peptide targeted to fibrin1,2 and apeptide-targeted nanoglobular agent.3 Important research has also beenpublished regarding our understanding of relaxivity, providing a pathfor incremental improvements in relaxivity of current gadolinium-based agents.4,5

Nanotechnology and other approaches have the potential toprovide an improvement in relaxivity for MR agents on the order of1000-fold, when compared with current agents.6 Our understandingof chemistry and structures has advanced to the extent that the devel-opment of such agents is possible. This would enable targeted appli-cations analogous to radioactive tracers, the use of much higher dosesthan that in practice today for the gadolinium chelates (90.1 mmol/kg),and a marked improvement in the safety profile of gadolinium chelatesoverall, with routine use allowing markedly lower doses of gadoliniumion to be administered. Multimodal agents7 and theragnostic agents8

(agents with combined diagnostic and therapeutic use) are also in de-velopment, with the latter, in particular, a major current area of inves-tigation, and likely to remain so for the next decade.

Chelate stability, high-dose administration, and gadoliniumion retained in the body have become areas of great concern in recentyears, given the advent of nephrogenic systemic fibrosis.9,10 Thisdisease, discovered and linked to the administration of the less-stablegadolinium chelates in patients with renal dysfunction, continues

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Received for publication May 25, 2013; and accepted for publication, after revision,June 4, 2013.

From the University Hospital Zurich, Switzerland.Conflicts of interest and sources of funding: none declared.Reprints: Val M. Runge, MD, University Hospital Zurich, Switzerland. E-mail:

[email protected] * 2013 by Lippincott Williams & WilkinsISSN: 0020-9996/13/4812Y0869

Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

mailto:[email protected]

to impact the field. As a consequence, the use of the agents mostlikely to cause this disease, such as gadodiamide (Omniscan, GEHealthcare),11 has markedly decreased, with withdrawal of theseagents likely from the market.

Magnetic Resonance AngiographySignificant advances are continuing to be made in MRA, for

techniques both with and without intravenous contrast use. The adventof nephrogenic systemic fibrosis spurred research in noncontrast MRA,with these techniques robust in widespread applications today,12Y15 al-though, in general, more time-consuming and of lower diagnosticquality when compared with contrast-enhanced techniques. Low-dosecontrast-enhanced techniques have similarly gained interest.16 The de-velopment of imaging techniques allowing image acquisition duringcontinuous table motionwas critical to the development ofMR positronemission tomography (PET), discussed in depth later, with the devel-opment of continuously moving table CE-MRA thus also enabled.17

Flow-sensitive 4-dimensional phase contrast is an important innova-tion, revealing altered flow patterns that may be missed by traditionalanalysis.18 Time-resolved techniques were first introduced more than10 years ago and provide, in current advanced implementations, criticaldiagnostic information otherwise not available.19,20 These techniquesare likely among the first to benefit from the developments in com-pressed sensing in the future. Preliminary work has already been shownwith techniques that can acquire greater than 10-foldYaccelerated dy-namic CE-MRA volumes with similar spatial resolution to that of cur-rent breath-hold techniques.21 Compressed sensing holds great promisefor improving both temporal and spatial resolution in CE-MRA.

BrainBrain MR imaging is often considered to be technologically

mature; however, in fact, this area, like all anatomic areas in MR, isseeing substantial improvements and will continue to so evolve overthe next decade. Diffusion-weighted imaging was first introduced forthe visualization of cytotoxic edema (in early brain ischemia) andwas thought, for many years, to be of little other utility. Like all MRparameters, diffusion lends itself to evaluation of many anatomic re-gions and disease processes, only that it was limited in early applica-tion because of problems with image acquisition. Bulk susceptibilityartifacts, due to the use of single-shot echo planar technique, repre-sented the major impediment to greater use across anatomic areas and,indeed, improved brain imaging. Multiple techniques have been de-veloped in recent years to limit bulk susceptibility effects,22Y24 withthe most important being the introduction of a readout-segmentedechoplanar imaging (rs-EPI) technique.25 The result, clinically, is avast improvement in image quality, reducing substantially bulk sus-ceptibility artifacts along with image blur. This approach can be

extended through simultaneous multislice acquisition and furtherthrough 3-dimensional (3D) multislab acquisition.26 Although thecurrent 3D acquisition requires an 11-minute scan, the spatial resolu-tion is 1.5-mm isotropic, with several viable approaches for a reductionin scan time while maintaining the requisite signal-to-noise ratio(SNR). The recent introduction of a 64-channel head-neck array coil at3 T further extends this approach, making possible simultaneousdiffusion-weighted MR of the brain and cervical spinal cord.27 Al-though clinical imaging is already currently being performed in areasoutside the brain, for example, the globes (and, indeed, in generalbody imaging; eg, MR-PET covered later in this article),28 withnonsegmented single shot EPI diffusion-weighted imaging (DWI), theavailability of these new techniques, and in particular rs-EPI, will fur-ther improve clinical image quality and utility.

It is commonly assumed in clinical practice that all brain me-tastases are visualized after intravenous contrast administration. Sub-stantial indirect evidence exists in the published literature that thisconclusion is false, specifically studies showing additional metastaseswith high-dose contrast administration (0.3 mmol/kg of gadoliniumchelate), and improved visualization of contrast enhancement with iso-tropic, high-resolution 3D imaging and at 3 T (as compared with 1.5 T).A basic research publication in 2011, evaluating brain metastases frombreast cancer in a mouse model, established that metastases, in particularsmaller lesions, may not manifest permeability of the blood-brain bar-rier.29 In 2013, another investigation emphasized the point that techniqueis critical for the identification of abnormal contrast enhancement and,thus, smaller brain metastases in clinical practice (Fig. 1). Specifically,3D MP-RAGE (magnetization-prepared rapid gradient echo, a gradientechoYbased technique), which is commonly used in clinical practiceafter contrast, was shown to be inferior for lesion detection as comparedwith 3D SPACE (sampling perfection with application optimized con-trasts by using different flip angle evolutions, a spin echoYbased tech-nique), with the 2 scans compared for identical acquisition time andvoxel size.30

Three articles published in 2012 to 2013 emphasized newscan approaches for brain imaging, providing either additional in-formation in specific disease entities or information not previouslyavailable by MR. A 3D T1-weighted double inversion magnetization-prepared rapid gradient echo sequence (MP2RAGE) was applied inpatients with multiple sclerosis (MS) and determined to outperformMP-RAGE for lesion contrast-to-noise ratio, count, and volume as-sessment.31 This approach also provides quantitative T1-relaxationtime maps, allowing better discrimination of lesion subtypes and stag-ing of lesion activity. A 3D T1-weighted dynamic contrast-enhancedMR (DCE-MR) imaging acquisition, with high spatial and temporalresolution, was developed and combined with 2-compartment model-ing for the quantification of cerebral blood flow, cerebral blood volume,

FIGURE 1. Improved MR imaging technique for visualization of abnormal contrast enhancement and, thus, identification of smallbrain metastases. SPACE, a fast spin echoYbased high-resolution 3D technique, offers in its current implementation greatersensitivity to lesion enhancement, as illustrated on the left-hand image for a lesion involving the anterior low frontal lobe(arrow). This metastasis was not visualized on the equivalent MP-RAGE acquisition, presented on the right, a gradient echoYbasedtechnique. Adapted from Reichert et al.30

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870 www.investigativeradiology.com * 2013 Lippincott Williams & Wilkins


and permeability surface area product.32 This was applied in patientswith MS for quantitative assessment, without prior knowledge of ana-tomic location, of both MS lesions and normal-appearing white matter.And equally innovative and potentially important, a cardiac-gatedphase contrast technique was optimized and used to estimate intracra-nial pressure in children with shunt-treated hydrocephalus. This ap-proach was validated and provides a promising tool for quantifyingintracranial pressure throughMR, with anticipation of an important rolein patients with suspected shunt malfunction.33

LiverIn recent years, techniques have been developed to quantitate

intrahepatic lipid (IHL) through MR rapidly, accurately, and with rel-ative ease, which are now available clinically.34 Such information is ofincreasing value in the modern world, because of obesity, with IHLknown to provide a better measure of obesity than previously usedmeasures such as body mass index or skinfold thickness. The assess-ment of IHL assumes an increasing importance for the evaluation ofpatients with obesity, with elevated IHL an important precursor for thedevelopment of insulin resistance and type 2 diabetes. The techniquesavailable today in MR, for the assessment of IHL, provide accuratemeasurements and are not confounded by the presence of liver iron,inflammation, or fibrosis/cirrhosis.35Y37

The field of MR is also on the verge of substantial improve-ments in 3D liver imaging, based, in part, on new developments inparallel imaging and echo sharing. For the past decade, parallel im-aging has largely relied upon the acquisition technique generalizedautocalibrating partially parallel acquisition (GRAPPA). A new parallelacquisition technique, controlled aliasing in parallel imaging resultsin higher acceleration (CAIPIRINHA), has recently been introducedand provides significantly higher image quality, with less parallelimaging artifacts and superior SNR. What, in the past, has routinelybeen a 20-second acquisition (conventional breath-hold liver imag-ing) may indeed, in the near future, be replaced by a 10-second ac-quisition, with many other variants possible because of the improvedparallel imaging performance in combination with higher SNR.38

Combining CAIPIRINHA with view sharing and Dixon water-fatseparation leads to a robust new approach for dynamic imaging ofthe upper abdomen, which provides both high temporal and spatialresolution.39 This approach yields reliable dynamic information, notsubject to contrast bolus timing issues, with improved lesion detect-ability (eg, in the arterial phase) and visualization of contrast kinet-ics (with calculation of quantitative perfusion measures) for focallesions. Such techniques may also prove useful for imaging ofthe breast, pelvis, and extremities. Another direction of develop-ment concerns solutions for liver perfusion imaging, similarly re-quiring high temporal and spatial resolution, but with the need to be

FIGURE 2. Current orthopedic MR investigation is focused on the development of improved imaging of soft tissues adjacent tometal (after implantation of metal prostheses or fixation devices). Images of a phantom containing a single stainless steelscrew are presented. The images are all proton densityYweighted and obtained with conventional (A), VAT (B), SEMAC (C), andSEMAC-VAT (D) techniques. E to H, The sagittal reformatted images corresponding to A to D: SEMAC-VAT allows for the bestartifact correction, as compared with VAT and SEMAC alone, for both in-plane and through-plane geometric distortions. Thefrequency-encoding direction was from top to bottom and parallel to the main magnetic field (white arrow). Adapted from Ai et al.47

Investigative Radiology & Volume 48, Number 12, December 2013 Current Technological Advances in MR

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acquired during free breathing and without view sharing, for high datafidelity.40

KidneyIn the last 5 years, blood oxygen levelYdependent (BOLD)

MR measurements of the renal cortex and medulla have been in-vestigated in regard to providing a measurement of tissue oxygena-tion applicable to human disease. 3 T, when compared with 1.5 T,more effectively detects developing parenchymal injury related toimpaired oxygenation.41 On the basis of animal studies, BOLD MRmay prove useful in diabetes, in which hypoxia is thought to be animportant factor, evaluating renal oxygenation and monitoring ther-apeutic intervention based on improving tissue hypoxia and prevent-ing progression of renal disease.42 Recent investigation has focusedon improving the analysis of renal BOLD data, proposing an approachthat is less labor-intensive and less prone to errors.43 Prospective nav-igation has also been recently demonstrated with BOLD, allowinglonger imaging times and an unprecedented improvement in spatialresolution and SNR, furthering the potential of this technique for theassessment of chronic kidney disease.44

Other MR techniques are being developed as well for the evalu-ation of renal function. This includes the use of low-dose DCE-MR toassess glomerular filtration rate. A recent study has shown that this ap-proach is suitable to evaluate functional loss in partial nephrectomies andcompensatory increase in renal function in the contralateral kidney.45

Musculoskeletal SystemImaging of the musculoskeletal system is being advanced by

both the introduction of improved scan sequences (predominantly 3Dacquisitions)46 together with a renewed emphasis on the developmentof scan techniques that reduce metal artifacts.47,48 Substantial prog-ress has already been achieved to date in terms of the development andclinical introduction of metal artifact reduction techniques (Fig. 2),which are critical for imaging of the postoperative patient, for detectionof infection, prosthesis loosening, and periprosthetic bony fractures.A major limitation, however, to novel techniques for reducing metalartifact, such as slice encoding for metal artifact correction (SEMAC),is scan time. SEMAC is a good candidate for acceleration using com-pressed sensing in part because the additional dimension acquired isinherently sparse. This approach was recently shown to allow imageacquisition for the knee, with an orthopedic prosthesis in place, in aclinically acceptable scan time of 5 minutes.49

BreastBreast MR imaging continues to make strides in terms of

improved lesion detection and diagnosis. 3 T, when compared with1.5 T, offers improved spatial resolution and also temporal resolutionfor dynamic studies.50 In the United States, 3 T imaging of the breasthas largely replaced 1.5 T, in centers where state-of-the-art scannerswith both field strengths are available. Dense breasts represent achallenge for mammography, and MR in this population should beconsidered for routine evaluation. When compared with mammog-raphy and ultrasound, MR detected more malignant lesions and led tofewer misdiagnoses in this population.51 In a multicenter Italianstudy published in 2011, MR was shown to outperform both mam-mography and ultrasonography, whether used separately or in com-bination, for screening women at high risk for breast cancer, whetheryounger or older than 50 years.52 Breast MR is so impressive in termsof lesion visualization that, on the basis of a 2012 study, it isrecommended for all patients with known breast cancer for stagingand surgical planning, positively affecting patient management withthe recurrence rate at long-term follow-up low.53 Current investiga-tion in the breast has focused on the value of DWI54 and DCE-MR,55

with elevation of parameters from the latter associated with shortersurvival and providing superior prognostic information to traditionalclinical indicators.56

ProstateProstate MR continues to be an active area of research, with

increasing clinical applicability. By 2009, the value of apparent dif-fusion coefficient (ADC) and, to a lesser extent, that of quantitativeT2 measurement were evident for assessing cell density in the pros-tate, suggesting the utility of these parameters for assessing tumoraggressiveness.57 Research published in 2010 extended the utility ofADC values to pelvic lymph nodes in prostate carcinoma, suggestingimproved ability to discriminate between benign and malignant nodeswhen compared with size criteria.58 Dynamic contrast-enhanced MR59

and proton spectroscopy were evaluated and determined to be of valuesoon thereafter in discriminating cancer from benign tissue,60 leading toa publication in 2012 comparing the relative value of the different MRparameters available (T2, DWI, DCE-MR, and proton spectroscopy).All parameters were shown to be of value in separating cancerfrom noncancer areas, in the peripheral zone of the prostate, withADC as the best single parameter. Proving the diagnostic accuracyof multiparametric MR imaging at 3 T and determination of the

FIGURE 3. A cancer-suspicious region in the left peripheral zone of the prostate is identified on T2-weighted (A), dynamiccontrast-enhanced (B), and diffusion-weighted (C) MR images at 3 T in a 62-year-old man. The lesion demonstrates discretehypointensity in A, hyperperfusion on the dynamic contrast-enhanced scan, and hypointensity on DWI (with hypointensityon the ADC map, not shown). In patients eligible for active surveillance, DWI shows promise for risk stratification, identifying andtargeting prostate carcinoma for biopsy, assisting in determining Gleason grade, and preventing undergrading. Adaptedfrom Somford et al.64




parameters contributing most to prostate cancer detection and lo-calization is the focus of an ongoing multicenter study.61 Recentclinical studies have focused on diffusion-weighted MR, highlight-ing its importance for predicting the presence of high-grade tumorand clarifying its role (Fig. 3).62Y65 Computation of DWI with higherb values than those typically acquired, due to time and SNR con-straints, offers an additional refinement of clinical technique.66

Interventional MRFive to 10 years ago, magnet technology was sufficient to support

development of the field of interventional MR, in particular with theintroduction of the initial generation of short, wide-bore 1.5-T systems.However, the development of the hardware needed in the MR environ-ment was not sufficiently mature at that time, with substantial problemsstill to be overcome because of the main magnetic field, the gradients,and radiofrequency excitation. In 2009, a total of 2 articles describingthe first truly MR-compatible guidewires were published. Both usedpassive marking concepts and demonstrated good visibility, with han-dling characteristics (stiffness, flexibility, steerability, and pushability)comparable with current guidewires in x-rayYbased angiography.67,68

Feasibility studies appeared as early as 2003 regarding MRimagingYguided high-intensity focused ultrasound (MR-HIFU) abla-tion,69 specifically for the treatment of symptomatic uterine fibroids. By

2011, thousands of cases had been performed and scientific investiga-tion was focused on the prediction of treatment outcome. Magneticresonance offers many ways to assess tissue properties, with DCE-MRshown to be of utility for predicting ablation efficacy. Specifically, ina 2011 published study,70 a high Ktrans at baseline was shown to bepredictive of a poor treatment result, suggesting the use of higheracoustic power in such patients.

Because of the significance of this emerging field (interven-tional MR), the June 2013 issue of Investigative Radiology was ded-icated to this subject. Interventional MR offers the advantages(compared with computed tomography [CT] and x-rayYbased ap-proaches) of superior soft-tissue contrast, rapid multiplanar imaging,real-time guidance and monitoring, temperature mapping, and theabsence of ionizing radiation (Fig. 4). At the current time, therapyis being performed under MR guidance in clinical routine usingcryoablation,71 high-intensity focused ultrasound,72,73 radiofrequencyablation,74 and laser thermotherapy.75,76 This is a dynamic, evolvingfield, with some techniques well established for specific indications;in other areas, there are options with respect to treatment approach,with no therapy yet established as that of choice.

Tissue biopsy for the diagnosis of malignant disease is, today,also routinely performed under MR guidance,77 with many indications,in particular for the breast and prostate.

FIGURE 4. A small cholangiocellular carcinoma metastasis (arrow) to the liver is illustrated before treatment on enhancedT1-weighted (A) and after MR-guided radiofrequency ablation on enhanced T1-weighted (B), unenhanced T1-weighted (C), andT2-weighted (D) images. For tumor ablation,MR offers advantages over both CT and ultrasound because of higher lesion sensitivity,the ability to actively monitor the ablation with multiple sequences and in 3 dimensions, and the ability to measure tissuetemperature (during the procedure). For identification of the ablated region, immediate posttreatment contrast enhancedT1-weighted scans serve as the accepted standard. Adapted from Rempp et al.74




An additional area of research is that of improving visualiza-tion of surgical implants on MR.78 In the short time span from 2010to 2013, this area of investigation has proceeded from concept toanimal evaluation79 to assessment in humans.80 Magnetic resonanceoffers, for the first time, a realistic approach to the evaluation ofimplants after surgery because of the high soft tissue contrast of themodality and the lack of ionizing radiation. Particularly in the initialarea investigated, that of surgery for inguinal hernias, MR may proveinvaluable for postsurgical assessment and evaluation of potentialcomplications therein, including deformation, shrinkage, migration,or adhesions. This likely represents simply one application of many

in the future, for the postoperative assessment of therapeutic success,with the eventual widespread development and use of easily MR-visualized surgical material.

MR-PETFor those who saw the development of CT, then MR, and then

subsequently PET-CT, the advent of MR-PET is significant andpresages a major new diagnostic modality. MR-PET required 2 im-portant, nontrivial, technologic advances: (1) the ability to do whole-body MR imaging with high spatial resolution and (2) integration ofPET detectors in the MR environment. Acquiring MR images during

FIGURE 5. Bony metastases from a pheochromocytoma are visualized on scans obtained using an integrated whole-body 3-TMR-PET system, with 18F-fluorodeoxyglucose used as the radiotracer. Illustrated are a coronal T1-weighted scan (A), maximumintensity projections of the PET data set in the coronal (B) and sagittal (C) views as well as fused MR-PET views in the coronal (D),sagittal (E), and axial (F) planes. Multiple tracer-avid bony lesions are identified, particularly in the spine, ribs, and pelvis. Adaptedfrom Quick et al.85




table movement represented a new paradigm, but by 2009, work wasalready being performed with whole-body MR for tumor staging.During this time frame, it also became evident that whole-body DWIwould play an important role in tumor evaluation, setting the stage forwhole-body screening by MR with PET to include T1-, T2-, anddiffusion-weighted scans.81 It was soon shown that DWI, specificallywith calculation of ADCs, held value as well for the assessment oftreatment response in whole-body tumor MR imaging.82 It may wellbe the case that MR-PET eclipses PET-CT in time, in clinical prac-tice, because of the value of available additional parameters, DWI inparticular, and because of image acquisition (MR and PET) beingtruly synchronous.83

MR-PET combines the high sensitivity of PET with that ofcontrast-enhanced MR and its intrinsic high spatial resolution. Thedevelopment of MR-PET has been technically challenging, and wewill likely see very rapid evolution of this technology in the next 5 to10 years. However, such hybrid systems, in which the acquisition ofMR and PET images is truly synchronous,84 have major diagnosticadvantages over PET-CT in instances where MR outperforms CT(because of improved soft tissue contrast and reduced radiationdose). Hybrid MR-PET is feasible today with early clinical units,with detection rates similar to PET-CT, with attenuation correctionperformed at this time using Dixon sequences.85 The clinical poten-tial of MR-PET is clear in oncology (Fig. 5), neurology, and cardi-ology,86 with major additional potential advantages in special patientpopulations, for example, pediatrics, breast carcinoma, and prostatecarcinoma. It should be kept in mind, however, that MR-PET is still veryearly in its development, with imaging approaches87 and coil technol-ogy88 still in rapid evolution. Early investigation in MR-PET for imag-ing of the prostate shows great promise, combining the high resolutionof MR with molecular imaging, leading to increased diagnosticconfidence in identifying and localizing prostate carcinoma.89 Aninitial small patient series, comparing MR-PET and PET-CT, using68-gallium-DOTA-D-Phe1-Tyr-octreotide in patients with knowngastroenteropancreatic neuroendocrine tumors showed improvedsensitivity for MR in identifying patients with malignant lesions,with known weaknesses inherent to MR, including specifically lungmetastases and sclerotic bone lesions.90 However, early investigationof areas considered as pitfalls for MR-PET, such as pulmonarynodules, shows success in overcoming potential problems and, thus,its integration into whole-body imaging.91 In an additional largerpatient series with 68-gallium-DOTA-D-Phe1-Tyr-octreotide, ana-tomic correlates for focal PET lesions could more often be delineatedon MR than on low-dose CT, with coregistration of data superior onMR-PET as well.92 Because of the significance of this emergingmodality, the May 2013 issue of Investigative Radiology was dedi-cated to this subject.

CONCLUSIONSAs a major field within diagnostic radiology, MR continues to

make rapid technological progress. Critical advances made in thepast 5 years have major impact for current clinical diagnosis andportend as well future important developments. The domination ofthis topic, with more than 60% of published manuscripts in Investiga-tive Radiology during 2009 to 2013 involving MR, reflects a vibrantresearch field. Continuing important developments in hardware andsoftware are evident in many areas, with specific focus areas includingthe gradient systems, radiofrequency transmitter, and innovative pulsesequences, in particular the implementation of compressed sensing.

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21. Rapacchi S, Fei H, Natsuaki Y, et al. High spatial and temporal resolutiondynamic contrast-enhanced magnetic resonance angiography (CE-MRA)using compressed sensing with magnitude image subtraction. InternationalSociety for Magnetic Resonance in Medicine, 21st Annual Meeting & Ex-hibition, 22Y26 April 2013, Salt Lake City, UT:0542.

22. Fries P, Runge VM, Kirchin MA, et al. Diffusion-weighted imaging in patientswith acute brain ischemia at 3 T: current possibilities and future perspectivescomparing conventional echoplanar diffusion-weighted imaging and fast spinecho diffusion-weighted imaging sequences using BLADE (PROPELLER).Invest Radiol. 2009;44:351Y359.

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32. Ingrisch M, Sourbron S, Morhard D, et al. Quantification of perfusion and per-meability in multiple sclerosis: dynamic contrast-enhanced MRI in 3D at 3T.Invest Radiol. 2012;47:252Y258.

33. Muehlmann M, Koerte I, Laubender R, et al. MR-based estimation of intra-cranial pressure correlates with VP-shunt valve opening pressure setting inchildren with hydrocephalus. Invest Radiol. 2013;48:543Y547.

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54. Baltzer P, Bogner W, Bickel H, et al. Is assessment of breast tumors with thesole use of dwi sufficient for breast cancer diagnosis? International Society forMagnetic Resonance in Medicine, 21st Annual Meeting & Exhibition, 22Y26April 2013, Salt Lake City, UT:3381.

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57. Gibbs P, Liney GP, Pickles MD, et al. Correlation of ADC and T2 measurementswith cell density in prostate cancer at 3.0 Tesla. Invest Radiol. 2009;44:572Y576.

58. Eiber M, Beer AJ, Holzapfel K, et al. Preliminary results for characterizationof pelvic lymph nodes in patients with prostate cancer by diffusion-weightedMR-imaging. Invest Radiol. 2010;45:15Y23.

59. Yakar D, Hambrock T, Huisman H, et al. Feasibility of 3T dynamic contrast-enhanced magnetic resonance-guided biopsy in localizing local recurrence ofprostate cancer after external beam radiation therapy. Invest Radiol. 2010;45:121Y125.

60. Scheenen TW, Futterer J, Weiland E, et al. Discriminating cancer fromnoncancer tissue in the prostate by 3-dimensional proton magnetic resonancespectroscopic imaging: a prospective multicenter validation study. InvestRadiol. 2011;46:25Y33.

61. Maas MC, KoopmanMJ, Litjens GJS, et al. Prostate Cancer Localization with aMultiparametric MR Approach (PCaMAP): Initial Results of a Multi-CenterStudy. International Society for Magnetic Resonance in Medicine, 21st An-nual Meeting & Exhibition, 22Y26 April 2013, Salt Lake City, UT:1769.

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64. Somford DM, Hoeks CM, Hulsbergen-van de Kaa CA, et al. Evaluation ofdiffusion-weighted MR imaging at inclusion in an active surveillance protocolfor low-risk prostate cancer. Invest Radiol. 2013;48:152Y157.

65. Nagel KN, Schouten MG, Hambrock T, et al. Differentiation of prostatitis andprostate cancer by using diffusion-weighted MR imaging and MR-guided bi-opsy at 3 T. Radiology. 2013;267:164Y172.

66. Maas MC, Fuetterer JJ, Scheenen TWJ. Quantitative evaluation of computedhigh b value diffusion weighted magnetic resonance imaging of the prostate.Invest Radiol. 2013;48:779Y786.

67. Kos S, Huegli R, Hofmann E, et al. Feasibility of real-time magnetic resonance-guided angioplasty and stenting of renal arteries in vitro and in swine, using anew polyetheretherketone-based magnetic resonance-compatible guidewire.Invest Radiol. 2009;44:234Y241.

68. Kramer NA, Kruger S, Schmitz S, et al. Preclinical evaluation of a novel fibercompound MR guidewire in vivo. Invest Radiol. 2009;44:390Y397.

69. Tempany CM, Stewart EA, McDannold N, et al. MR imaging-guided focusedultrasound surgery of uterine leiomyomas: a feasibility study. Radiology. 2003;226:897Y905.

70. KimYS, LimHK, Kim JH, et al. Dynamic contrast-enhancedmagnetic resonanceimaging predicts immediate therapeutic response of magnetic resonance-guidedhigh-intensity focused ultrasound ablation of symptomatic uterine fibroids.Invest Radiol. 2011;46:639Y647.

71. Ahrar K, Ahrar JU, Javadi S, et al. Real-time magnetic resonance imaging-guided cryoablation of small renal tumors at 1.5 T. Invest Radiol. 2013;48:437Y444.

72. Napoli A, Anzidei M, Cavallo Marincola B, et al. Primary pain palliation andlocal tumor control in bone metastases treated with magnetic resonance-guidedfocused ultrasound. Invest Radiol. 2013;48:351Y358.

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75. Vogl TJ, Freier V, Nour-Eldin NE, et al. Magnetic resonance-guided laser-induced interstitial thermotherapy of breast cancer liver metastases and othernoncolorectal cancer liver metastases: an analysis of prognostic factors forlong-term survival and progression-free survival. Invest Radiol. 2013;48:406Y412.

76. Oto A, Sethi I, Karczmar G, et al. MR imaging-guided focal laser ablation forprostate cancer: phase I trial. Radiology. 2013;267:932Y940.

77. Lu Y, Fritz J, Li C, et al. MR imaging-guided percutaneous biopsy of medi-astinal masses: diagnostic performance and safety. Invest Radiol. 2013;48:452Y457.

78. Kramer NA, Donker HC, Otto J, et al. A concept for magnetic resonancevisualization of surgical textile implants. Invest Radiol. 2010;45:477Y483.

79. Kraemer NA, Donker HC, Kuehnert N, et al. In vivo visualization of polymer-based mesh implants using conventional magnetic resonance imaging andpositive-contrast susceptibility imaging. Invest Radiol. 2013;48:200Y205.

80. Hansen NL, Barabasch A, Distelmaier MS, et al. First in-human MR-visualisationof surgical mesh implants for inguinal hernia treatment. Invest Radiol. 2013;48:770Y778.

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82. Lin C, Itti E, Luciani A, et al. Whole-body diffusion-weighted imaging with ap-parent diffusion coefficient mapping for treatment response assessment in patientswith diffuse large B-cell lymphoma: pilot study. Invest Radiol. 2011;46:341Y349.

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