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MR imaging at high magnetic fi elds Masaya Takahashi a Hidemasa Uematsub Hiroto Hatabua aDepartment of Radiology Beth Israel Deaconess Medical Center Boston MA 02115 USA bDepartment of Radiology University of Pennsylvania Medical Center Philadelphia PA USA Received 12 November 2002 received in revised form 13 November 2002 accepted 14 November 2002 Abstract Recently more investigators have been applying higher magnetic field strengths 3 4 Tesla in research and clinical settings Higher magnetic field strength is expected to afford higher spatial resolution and or a decrease in the length of total scan time due to its higher signal intensity Besides MR signal intensity however there are several factors which are magnetic field dependent thus the same set of imaging parameters at lower magnetic field strengths would provide differences in signal or contrast to noise ratios at 3 T or higher Therefore an outcome of the combined effect of all these factors should be considered to estimate the change in usefulness at different magnetic fields The objective of this article is to illustrate the practical scientific applications focusing on MR imaging of higher magnetic field strength First we will discuss previous literature and our experiments to demonstrate several changes that lead to a number of practical applications in MR imaging e g in relaxation times effects of contrast agent design of RF coils maintaining a safety profile and in switching magnetic field strength Second we discuss what will be required to gain the maximum benefit of high magnetic field when the current magnetic field 5 1 5 T is switched to 3 or 4 T In addition we discuss MR microscopy which is one of the anticipated applications of high magnetic field strength to understand the quantitative estimation of the gain benefit and other considerations to help establish a practically available imaging protocol 2002 Elsevier Science Ireland Ltd All rights reserved Keywords Magnetic resonance imaging Higher magnetic fi eld strength Contrast agent 1 Introduction Thanks to recent technological development whole body magnetic resonance MR scanners at higher magnetic field strengths 3 T have been introduced into research and clinical settings In the beginning one of the main reasons to install higher fields was its higher sensitivity to the blood oxygenation level dependent effect for functional MR imaging of the brain 1 Recently more investigators applied these higher mag netic field strengths to both research and conventional clinical settings The expectation for higher magnetic fields in MRI is the improvement in signal to noise ratio SNR due to higher signal intensity SI where the most significant benefit is to decrease the length of time required to obtain images Then higher spatial resolu tion may be achievable One question is how it improves or practically how beneficial it is when we switch the current magnetic field 5 1 5 T to 3 or 4 T Several studies have reported and discussed the advantages of higher magnetic field in for example delineation of various brain lesions 1 or cardiac structures 2 3 Dougherty et al 2 reported that the SNR of the anterior myocardium at 4 T was 2 9 times higher than that of the same region at 1 5 T Bernstein et al demonstrated contrast enhanced imaging at 3 T and concluded that higher spatial resolution at 3 T could improve diagnostic accuracy 4 In addition if higher magnetic field can provide better image quality it may be reasonable to expect a reduction in total injection of contrast agent for example in MR angiography which needs to cover a larger area of the peripheral artery 5 or the lung 6 7 However such speculation would be difficult to prove as higher magnetic fields change other imaging aspects besides SNR Many theoretical and experimental studies have been employed to demonstrate the magnetic field dependen cies Besides SNR the magnetic field dependence is Corresponding author Tel 1 617 667 0198 fax 1 617 667 7021 E mail address mtakahas caregroup harvard edu M Takahashi European Journal of Radiology 46 2003 45 52 0720 048X 02 see front matter 2002 Elsevier Science Ireland Ltd All rights reserved PII S0720 048X 02 00331 5 well documented in tissue relaxation times 8 10 as well as in MR contrast agent effects e g R1 R2 or R2 relaxivities 11 12 SNR depends upon imaging para meters RF coil sensitivity and machine adjustments such as magnetic field homogeneity accuracy in excita tion refocusing pulse settings etc These theoretical and experimentally proven properties suggest that imaging parameters must be reconfigured for different magnetic fields Unlike relaxation time and MR contrast agent effects the benefit to signal intensity at higher magnetic field should be compared under nearly identical experi mental conditions Therefore it is imperative to quan tify the practical differences in terms of SNR and contrast to noise ratios CNR between higher and lower B 1 5 T magnetic fields However the studies of direct comparisons between SNRs and CNRs as an outcome of the combined effect of several magnetic field dependent parameters at different fields compared with the theoretical values are substantially sparse Hence it is still unclear how much benefit we can gain in SNR or what we can should do in switching a current magnetic field strength 5 1 5 T in most cases to a higher magnetic field In this article we consider the magnetic field dependent alterations e g MR signal on the image relaxation times effects of contrast agent design of RF coil and safety profile Then we evaluate the scientific expectations for MR imaging on a higher magnetic field to quantify the scientific and technical issues relative to safe human experimentation Further the feasibility of MR microscopy which is one of the expectations of higher fields is discussed 2 SI SNR and CNR The question of optimum field strength has been a subject of intense controversy for over a decade The interest in higher fields stems from the fact that SNRs increase with field strength v where SI and noise have different magnetic field dependencies SI8 number of spins voltage induced by each spin 1 As shown in Eq 1 theoretically the signal intensity from a MR experiment is proportional to the square of the static magnetic field v2 since both number of spins that can be observed and voltage induced by each spin increase linearly as magnetic field v increases Noise is proportional to the static magnetic field v when all noise comes from a sample resulting in an SNR that is proportional to v in the case On the other hand noise is proportional to one quarter of v v1 4 when all noise comes from the RF coil resulting in an SNR that is proportional to v7 4 Therefore SNR can be expected to increase more than 2 7 4 1 5 times at 4 than at 1 5 T If this is true since the SNR scales as the square root of the number of image averages the time needed to obtain the same SNR is reduced by a factor of 8 To confirm this theory we imaged the brain in a subject at both fields To make our comparison between the magnetic fields as direct as possible the same sets of experiments in the same subjects were conducted at both 4 and 1 5 T on the commercially supplied whole body MR scanners SignaTM General Electric Systems Mil waukee WI with the equipped head coils Fig 1 shows the T1 weighted images top and T2 weighted images bottom obtained in the same level of the brain of the same subject Each image was obtained with a conven tional spin echo sequence with the same imaging parameters at 1 5 and 4 T respectively These images showed different tissue contrast between the magnetic fields even though the images were acquired with the same set of imaging parameters In the quantitative measurements of SI we found that 4 T increased the SI in both white and gray matter Fig 1 In addition those enhancement ratios were also different between the imaging parameters T1 WI and T2 WI Thus 4 T provides a different tissue contrast compared with 1 5 T using the same set of imaging parameters which might be inconsistent with theoretical values 3 Relaxation times As discussed above SNR in biological tissue was found to be in approximate proportion to field strength However the practically achievable SNR gain may be somewhat less since the above theory assumes that all parameters except the magnetic field are consistent One reason for the discrepancy is the increase in T1 relaxa tion time with increasing field strength SI is a function of relaxation time that is in turn magnetic field dependent 3 In theory T1 value increases in a magnetic field dependent manner in most biological tissues of which the correlation time tc of tissue water is 10 8s 13 whereas T2 value does not change Fig 2 Comparisons of relaxation times in humans have been published in the literature Jezzard et al and Duewell et al presented a comparison of T1 and T2 relaxation times in human subjects between 1 5 and 4 T in the brain and several peripheral regions 9 10 Table 1 In any tissue T1 relaxation times are prolonged at a higher magnetic field while T2 relaxation times are somewhat shortening Those results are consistent with previous reports Fig 2 To confirm this phenomenon we conducted the same set of phantom experiments at both 4 and 1 5 T on the same whole body MR scanners with head coils 14 Phantoms included different con centrations of Gd complex aqueous solution with each phantom representing tissue with a different T1 relaxa M Takahashi et al European Journal of Radiology 46 2003 45 5246 tion time In this study the trains of spin echo images with varied TRs or TEs were obtained with the same commercial clinical scanners with the head coils de scribed above The relaxation times T1 T2 for all phantoms were determined at both 1 5 and 4 T from the fitting curves The results in this confirmatory study demonstrated that any T1 relaxation times were pro longed 1 10 1 47 times at 4 T compared with those at 1 5 T while T2 values were identical or slightly shortened Table 2 Further a standard contrast enhanced MR angio graphic sequence 3D spoiled gradient recalled acquisi tionorSPGR sequencewiththesameimaging parameters was utilized to confirm changes in SI Peak SNRs at 4 T increased at least 2 21 times higher compared with those at 1 5 T Moreover peak CNRs at 4 T increased at least 1 59 times higher compared with those at 1 5 T in the range of Gd concentrations expected during clinical use In addition those enhance ments of SNR and CNR were a function of a flip angle that we used Based on those results using higher Fig 1 T1 and T2 weighted images of a human subject obtained at 1 5 and 4 Tesla Each image was acquired with the same set of imaging parameters TR TE is indicated in the parentheses respectively Note that different magnetic fi elds provided different image contrast Fig 3 Cross sectional T1 weighted image of a fi xed excised spinal cord of the larval sea lamprey Image was obtained at 9 4 T experimental machine resolution was 9 9 mm resolution See Ref 27 Fig 2 Magnetic fi eld dependency in T1 and T2 relaxation times modifi ed from Ref 13 M Takahashi et al European Journal of Radiology 46 2003 45 5247 magnetic fields seems to be beneficial in CNRs as well as in SNRs even without optimization of imaging para meters at each magnetic field A relationship between the SI of a gradient echo sequence the relaxation time and the optimal flip angle ao Ernst angle can be expressed as follows SI b 1 exp TR T1 exp TE T2 sin a 1 exp TR T1 cos a 2 and cos ao exp TR T1 3 where b is the scaling factor and a is the flip angle SI is determined by its relaxation times T1 and T2 in individual tissue conditions in any imaging sequence This implies that the same intensity will not be obtained with the same set of imaging parameters due to the alternation of relaxation times at different magnetic field Since T1 values at higher magnetic field are longer than those at lower magnetic field the TR presumably as well as the flip angle should be longer smaller for flip angle to optimize the SNR of the same sample at the higher field Using longer TR the advantage in SI at a higher field would be less in unit time In other words since the primary limitation imposed by long T1 relaxation time at higher magnetic field strength is reflected in the TR the SNR per unit time is optimized with an Ernst angle pulse and the shortest achievable value of TR T1 The necessity of optimization of imaging parameters was presented in a previous work Keiper et al 15 compared the usefulness in the diagnosis of white matter abnormalities in multiple sclerosis patients following the optimization of imaging parameters between 1 5 and 4 T Their results demon strated that MR imaging at 4 T 512 256 matrix could depict smaller lesions that could not be detected at 1 5 T 256 192 matrix implying that the higher resolution at 4 T provides higher accuracy of diagnosis in the same patients with almost identical total scan time Although T2 values were substituted for T2 in the phantom study because T2 and T2 values should be theoretically identical in phantoms in each magnetic field 16 it is considered to be different from the conditions in some tissues where the T2 value is much shorter than the T2 value in some tissues A magnitude of susceptibility g is proportional to the magnetic field as shown in the following equation 17 g Dx 2 B0 RGz 4 where Dx is the difference in magnetic susceptibility of adjoining substances B0 v is the static magnetic field R is the cross section radius and Gzis the read out gradient However this effect on T2 depends on T2 in tissue since 1 T2 is a function of T2 and T2 R2 R2 R2 18 The shorter T2 and T2 values at a higher magnetic field may cause a larger decrease in the SNR and CNR than would be expected in some tissue such as the lung Previously we found that the CNR increased in the central arteries of the lung but did not increase in the pulmonary peripheral arteries at 4 T as the dose of contrast agent increased ranging from 0 05 to 0 2 mmol kg body weight 19 Therefore the optimal imaging parameters for the clinical application should be carefully considered particular when an undesirable T2 effect may be involved 4 Relaxivities of Gd complex The R1 relaxivity of MR contrast agent is dependent upon various parameters such as the type of contrast agent 20 temperature and tissue environment as well as magnetic field strength 11 12 R1 relaxivity of a paramagnetic contrast agent is higher at lower field strength 11 R2 and R2 values should be theoretically identical in phantoms in each magnetic field 16 In the phantom study described above the authors attempted to compare the effects of contrast agent For an accurate determination of the efficacy of Gd complex R1 R2 and R2 only some of the relaxation times Table 1 Comparison of T1 and T2 relaxation times in human subject 9 10 TissueT1 s T2 ms 1 5 T4 T1 5 T4 T Braina Gray matter0 9 1 3 1 7277 9063 White matter0 7 1 1 1 0462 8050 Muscleb0 981 833126 Fatb0 310 394738 Bone marrowb0 290 424742 a Lezzard et al 9 b Duewell et al 10 From previous literature Table 2 Comparison of T1 and T2 relaxation time in gadolinium doped water solution at room temperature modifi ed Ref 14 Gd concentration mmol l T1 ms T2 ms 1 5 T4 T1 5 T4 T 02556363616431504 0 12510671566911862 0 5419562348351 1 25191253160160 2 51231428483 567814342 At room temperature M Takahashi et al European Journal of Radiology 46 2003 45 5248 T1 T2 that could be excellently fitted to the curve r 0 995 were reciprocally plotted against the concentra tions of Gd at both 4 and 1 5 T As a result R1 and R2 relaxivity values were determined to be 2 95 and 4 82 l s 1 mmol 1 at 4 T and 3 89 and 4 67 l s 1 mmol 1 at 1 5 T respectively R1 at 4 T was lower 25 than R1 at 1 5 T while the R2 at 4 T was almost that at 1 5 T Table 3 Hence we found that R1 relaxivity decreases as the magnetic field strength increases while R2 relaxivity does not change as much which is consistent with previous reports 16 Unlike Gd complex R2 and R2 might be consider ably changed depending upon the type of contrast agent e g super paramagnetic iron oxide SPIO application root and or tissues This suggested that we should also consider the use of the MR contrast agent though it is not clear whether this change is substantially effective in current clinical usage at higher magnetic field 5 RF coil The application of higher magnetic field strengths to MR imaging particular in whole body imaging is more demanding because of the difficulty in building RF coils since the penetration of radio frequency into the tissue becomes harder 3 21 It is necessary to understand the relationship between SNR and RF coil since an incomplete RF coil may sacrifice the advantage in SNR at increased magnetic field strength RF coil characteristics especially a receive coil significantly impactSNR SNRincreaseswithdecreasingcoil diameter Thus the coil sensitivity of the head coil is 3 fold higher than that of the body coil The surface coilwithsmallerdiametergainsmoresensitivity whereas the SNR drops off very rapidly with increasing depth from the surface To cover these difficulties an array of surface coils must be developed Reported by Wright et al 22 another idea to increase coil sensitivity and further improve SNR is to reduce coil temperature thus lowering its resistance and thermal noise voltages and increasing its Q while keeping the sample at room temperature The cryogenic SNR gain would be greatest for coil and sample configurations having QL QUclose to 1 6 Safety consideration Theoretical calculations of the interaction of high magnetic fields with human subjects have been reviewed To date no hazardous physical or physiological phe nomena have been shown The mechanism considered included orientation of macromolecules and mem branes effects on nerve conduction electrocardiograms and electroencephalograms and blood flow The most current clinical MR imagers at lo