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This paper updates and extends three previous papers on tissue property filters (TP-filters), Multiplied, Added, Divided and/or Subtracted Inversion Recovery (MASTIR) pulse sequences and synergistic contrast MRI (scMRI). It does this by firstly adding the central contrast theorem (CCT) to TP-filters, secondly including division with MASTIR sequences to make them Multiplied, Added, Subtracted and/or Divided IR (MASDIR) sequences, and thirdly incorporating division into the image processing needed for scMR to increase synergistic T

BACKGROUND: T(1ρ) has been extensively reported as a sensitive biomarker of biochemical changes in the nucleus pulposus (NP) and annulus fibrosis of intervertebral discs (IVDs). However, no T(1ρ) study of cartilaginous endplates (CEPs) has yet been reported because the relatively long echo times (TEs) of conventional clinical T(1ρ) sequences cannot effectively capture the fast-decaying magnetic resonance signals of CEPs, which have very short T(2)/T(2)*s. This can be overcome by using ultrashort echo time (UTE) T(1ρ) acquisitions. METHODS: Seventeen subjects underwent UTE with adiabatic T(1ρ) preparation (UTE-Adiab-T(1ρ)) and T(2)-weighted fast spin echo imaging of their lumbar spines. Each IVD was manually segmented into seven regions (i.e., outer anterior annulus fibrosis, inner anterior annulus fibrosis, outer posterior annulus fibrosis, inner posterior annulus fibrosis, superior CEP, inferior CEP, and NP). T(1ρ) values of these sub-regions were correlated with IVD modified Pfirrmann grades and subjects’ ages. In addition, T(1ρ) values were compared in subjects with and without low back pain (LBP). RESULTS: Correlations of T(1ρ) values of the outer posterior annulus fibrosis, superior CEP, inferior CEP, and NP with modified Pfirrmann grades were significant (P

Background Center-out radial sampling of k-space in magnetic resonance imaging employs a different direction for each readout. Off-resonance artifacts (including those produced by chemical shift between water and fat) found with this type of sampling are usually described as blurring, however more specific characterization of these artifacts can be ascertained from the fact that their point spread function is ring-shaped. This produces effects that differ from those seen with Cartesian sampling of k-space. Experiments were designed to demonstrate the origin of these artifacts and a volunteer was imaged to show them. Methods Two phantoms containing oil in a syringe and an annulus of oil surrounded by water were scanned with a range of bandwidths from 62.5 down to 4 kHz. In a human volunteer, head, pelvis and spine images were obtained with bandwidths of 62.5 and 4 kHz. Results The two phantoms showed displacement of the oil signal away from the center into the region of the surrounding water. The effect increased as the bandwidth was decreased. In the head of the volunteer, signal from fat in red bone marrow in the skull was displaced centrally and peripherally relative to water within the marrow, and appeared in the region between the skull and the brain, as well as in the surrounding scalp. Displacements of the former type simulated subdural hematomas. Displacement of perivesical fat signal centrally over the wall of the bladder simulated bladder tumor, and displacement of fat signal from red bone marrow in the lumbar spine to the intervertebral discs simulated their cartilaginous endplates. Conclusions Center-out radial artifacts are important to recognize on clinical images since they may mimic anatomy and simulate pathology. The article shows how these artifacts originate, includes examples, and describes how the artifacts differ from Cartesian chemical shift artifacts.

Purpose To describe a new method for accurate T1 measurement of cortical bone that fits the data sets of both 3D UTE actual flip angle imaging (UTE-AFI) and UTE with a single TR (UTE-STR) simultaneously (UTE-AFI-STR). Theory and methods To make both the constant values and longitudinal mapping functions in the signal equations for UTE-AFI and UTE-STR identical, the same RF pulses and flip angles were used. Therefore, there were three unknowns in the three equations. This was sufficient to fit the data. Numerical simulation as well as ex vivo and in vivo cortical bone studies were performed to validate the T1 measurement accuracy with the UTE-AFI-STR method. The original UTE-AFI variable TR (VTR) (ie, combined UTE-AFI and UTE with VTR) and simultaneous fitting (sf) of UTE-AFI and UTE-VTR (sf-UTE-AFI-VTR) methods were performed for comparison. Results The numerical simulation study showed that the UTE-AFI-STR method provided accurate value of T1 when the SNR of the UTE-STR image was higher than 40. The ex vivo study showed that the UTE-AFI-STR method measured the T1 of cortical bone accurately, with difference ratios ranging from -5.0% to 0.4%. The in vivo study showed a mean T1 of 246 ms with the UTE-AFI-STR method, and mean difference ratios of 2.4% and 5.0%, respectively, compared with the other two methods. Conclusion The 3D UTE-AFI-STR method provides accurate mapping of the T1 of cortical bone with improved time efficiency compared with the UTE-AFI-VTR/sf-UTE-AFI-VTR methods.

Background Water signal contamination is a major challenge for direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the signals detected in white matter. Purpose To validate a new short repetition time (TR) adiabatic inversion recovery (STAIR) prepared UTE (STAIR-UTE) sequence designed to suppress water signals and to allow imaging of ultrashort T2 protons of myelin in white matter using a clinical 3-T scanner. Materials and Methods In this prospective study, an optimization framework was used to obtain the optimal inversion time for nulling water signals using STAIR-UTE imaging at different TRs. Numeric simulation and phantom studies were performed. Healthy volunteers and participants with multiple sclerosis (MS) underwent MRI between November 2018 and October 2019 to compare STAIR-UTE and a clinical T2-weighted fluid-attenuated inversion recovery sequence for assessment of MS lesions. UTE measures of myelin were also performed to allow comparison of signals in lesions and with those in normal-appearing white matter (NAWM) in patients with MS and in normal white matter (NWM) in healthy volunteers. Results Simulation and phantom studies both suggest that the proposed STAIR-UTE technique can effectively suppress long T2 tissues with a broad range of T1s. Ten healthy volunteers (mean age, 33 years ± 8 [standard deviation]; six women) and 10 patients with MS (mean age, 51 years ± 16; seven women) were evaluated. The three-dimensional STAIR-UTE sequence effectively suppressed water components in white matter and selectively imaged myelin, which had a measured T2* value of 0.21 msec ± 0.04 in the volunteer study. A much lower mean UTE measure of myelin proton density was found in MS lesions (3.8 mol/L ± 1.5), and a slightly lower mean UTE measure was found in NAWM (7.2 mol/L ± 0.8) compared with that in NWM (8.0 mol/L ± 0.8) in the healthy volunteers (P < .001 for both comparisons). Conclusion The short repetition time adiabatic inversion recovery-prepared ultrashort echo time sequence provided efficient water signal suppression for volumetric imaging of myelin in the brain and showed excellent myelin signal contrast as well as marked ultrashort echo time signal reduction in multiple sclerosis lesions and a smaller reduction in normal-appearing white matter compared with normal white matter in volunteers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Messina and Port in this issue.

The first metatarsophalangeal joint (MTPJ) is vital to the biomechanics of the foot and supports a weight up to eight times heavier than the body during athletic activities. The first MTPJ comprises osseous and cartilaginous surfaces along with a complex of supporting structures, including the dorsal extensor tendons, collateral ligaments, and a plantar plate complex. In contradistinction to the lesser MTPJ plantar plates, a single dominant fibrocartilaginous capsular thickening does not exist at the first MTPJ. Instead, the plantar plate complex comprises a fibrocartilaginous pad that invests the hallux sesamoids and is inseparable from the plantar capsule, the intersesamoid ligament, paired metatarsosesamoid and sesamoid phalangeal ligaments (SPLs), and the musculotendinous structures. Acute injury at the first MTPJ is typically secondary to forced hyperextension—turf toe—and can involve multiple structures. During hyperextension, the resulting forces primarily load the distal SPLs, making these structures more susceptible to injury. SPL injuries are best seen in the sagittal plane at MRI. Radiography can also aid in diagnosis of full-thickness SPL tears, demonstrating reduced sesamoid excursion at lateral dorsiflexed (stress) views. Hallux valgus is another common condition, resulting in progressive disabling deformity at the first MTPJ. Without appropriate treatment, first MTPJ injuries may progress to degenerative hallux rigidus. The authors detail the anatomy of the first MTPJ in cadaveric forefeet by using high-resolution 3-T and 11.7-T MRI and anatomic-pathologic correlation. Injuries to the plantar plate complex, collateral ligaments, and extensor mechanism are discussed using clinical case examples. Online supplemental material is available for this article. (©)RSNA, 2020

The group of Multiplied, Added, Subtracted and/or fiTted Inversion Recovery (MASTIR) pulse sequences in which usually two or more inversion recovery (IR) images of different types are combined is described, and uses for this type of sequence are outlined. IR sequences of different types can be multiplied, added, subtracted, and/or fitted together to produce variants of the MASTIR sequence. The sequences provide a range of options for increasing image contrast, demonstrating specific tissues and fluids of interest, and suppressing unwanted signals. A formalism using the concept of pulse sequences as tissue property filters is used to explain the signal, contrast and weighting of the pulse sequences with both univariate and multivariate filter models. Subtraction of one magnitude reconstructed IR image from another with a shorter TI can produce very high T(1) dependent positive contrast from small increases in T(1). The reverse subtracted IR sequence can provide high positive contrast enhancement with gadolinium chelates and iron deposition which decrease T(1). Additional contrast to that arising from increases in T(1) can be produced by supplementing this with contrast arising from concurrent increases in ρ(m) and T(2), as well as increases or decreases in diffusion using subtraction IR with echo subtraction and/or diffusion subtraction. Phase images may show 180º differences as a result of rotating into the transverse plane both positive and negative longitudinal magnetization. Phase images with contrast arising in this way, or other ways, can be multiplied by magnitude IR images to increase the contrast of the latter. Magnetization Transfer (MT) and susceptibility can be used with IR sequences to improve contrast. Selective images of white and brown adipose tissue lipid and water components can be produced using different TIs and in and out-of-phase TEs. Selective images of ultrashort and short T(2) tissue components can be produced by nulling long T(2) tissue components with an inversion pulse and subtraction of images with longer TEs from images with ultrashort TEs. The Double Echo Sliding IR (DESIRE) sequence provides images with a wide range of TIs from which it is possible to choose values of TI to achieve particular types of tissue and/or fluid contrast (e.g., for subtraction with different TIs, as described above, and for long T(2) tissue signal nulling with UTE sequences). Unwanted tissue and fluid signals can be suppressed by addition and subtraction of phase-sensitive (ps) and magnitude reconstructed images. The sequence also offers options for synergistic use of the changes in blood and tissue ρ(m), T(1), T(2)/T(2)*, D* and perfusion that can be seen with fMRI of the brain. In-vivo and ex-vivo illustrative examples of normal brain, cartilage, multiple sclerosis, Alzheimer’s disease, and peripheral nerve imaged with different forms of the MASTIR sequence are included.

This paper describes a quantitative approach to understanding the signal, contrast and weighting of magnetic resonance (MR) images. It uses the concept of pulse sequences as tissue property (TP) filters and models the signal, contrast and weighting of sequences using either a single TP-filter (univariate model) or several TP-filters (the multivariate model). For the spin echo (SE) sequence using the Bloch equations, voxel signal intensity is plotted against the logarithm of the value of the TPs contributing to the sequence signal to produce three TP-filters, an exponential ρ(m)-filter, a low pass T(1)-filter and a high pass T(2)-filter. Using the univariate model which considers signal changes in only one of ρ(m), T(1), or T(2) at a time, the first partial derivative of signal with respect to the natural logarithm of ρ(m), T(1) or T(2) is the sequence weighting for each filter (for small changes in each TP). Absolute contrast is then the sequence weighting multiplied by the fractional change in TP for each filter. For large changes in TPs, the same approach is followed, but using the mean slope of the filter as the sequence weighting. These approaches can also be used for fractional contrast. The univariate TP-filter model provides a mathematical framework for converting conventional qualitative univariate weighting as used in everyday clinical practice into quantitative univariate weighting. Using the multivariate model which considers several TP-filters together, the relative contributions of each TP to overall sequence and image weighting are expressed as sequence and imaging weighting ratios respectively. This is not possible with conventional qualitative weighting which is univariate. The same approaches are used for inversion recovery (IR), pulsed gradient SE, spoiled gradient echo (SGE), balanced steady state free precession, ultrashort echo time and other pulse sequences. Other TPs such as susceptibility, chemical shift and flow can be included with phase along the Y axis of the TP-filter. Contrast agent effects are also included. In the text TP-filters are distinguished from k-space filters, signal filters (S-filters) which are used in imaging processing as well as to describe windowing the signal width and level of images, and spatial filters. The TP-filters approach resolves many of the ambiguities and inconsistencies associated with conventional qualitative weighting and provides a variety of new insights into the signal, contrast and weighting of MR images which are not apparent using qualitative weighting. The TP-filter approach relates the preparation component of pulse sequences to voxel signal, and contrast between two voxels. This is complementary to k-space which relates the acquisition component of pulse sequences to the spatial properties of MR images and their global contrast.

Background Signal contamination from long T2 water is a major challenge in direct imaging of myelin with MRI. Nulling of the unwanted long T2 signals can be achieved with an inversion recovery (IR) preparation pulse to null long T2 white matter within the brain. The remaining ultrashort T2 signal from myelin can be detected with an ultrashort echo time (UTE) sequence. Purpose To develop patient-specific whole-brain myelin imaging with a three-dimensional double-echo sliding inversion recovery (DESIRE) UTE sequence. Materials and Methods The DESIRE UTE sequence generates a series of IR images with different inversion times during a single scan. The optimal inversion time for nulling long T2 signal is determined by finding minimal signal on the second echo. Myelin images are generated by subtracting the second echo image from the first UTE image. To validate this method, a prospective study was performed in phantoms, cadaveric brain specimens, healthy volunteers, and patients with multiple sclerosis (MS). A total of 20 healthy volunteers (mean age, 40 years ± 13 [standard deviation], 10 women) and 20 patients with MS (mean age, 58 years ± 8; 15 women) who underwent MRI between November 2017 and February 2019 were prospectively included. Analysis of variance was performed to evaluate the signal difference between MS lesions and normal-appearing white matter in patients with MS. Results High signal intensity and corresponding T2* and T1 of the extracted myelin vesicles provided evidence for direct imaging of ultrashort-T2 myelin protons using the UTE sequence. Gadobenate dimeglumine phantoms with a wide range of T1 values were selectively suppressed with DESIRE UTE. In the ex vivo brain study of MS lesions, signal loss was observed in MS lesions and was conformed with histologic analysis. In the human study, there was a significant reduction in normalized signal intensity in MS lesions compared with that in normal-appearing white matter (0.19 ± 0.10 vs 0.76 ± 0.11, respectively; P < .001). Conclusion The double-echo sliding inversion recovery ultrashort echo time sequence can generate whole-brain myelin images specifically with a clinical 3-T scanner. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Port in this issue.

PURPOSE: To develop a new myelin water imaging (MWI) technique using a short TR adiabatic inversion recovery (STAIR) sequence on a clinical 3T MR scanner. METHODS: Myelin water (MW) in brain has both a much shorter T(1) and a much shorter T(2)* than intra/extracellular water. A STAIR sequence with a short TR was designed to efficiently suppress long T(1) signals from intra/extracellular water and so allow selective imaging of MW which has a much shorter T(1). Numerical simulation and phantom studies were performed to investigate the effectiveness of long T(1) signal suppression. T(2)* in white matter (WM) was measured with STAIR and compared with T(2)* measured with a conventional GRE in in vivo study. Four healthy volunteers and four patients with multiple sclerosis (MS) were recruited for qualitative and quantitative MWI. Apparent MW fraction (aMWF) was generated to compare MW in normal WM (NWM) in volunteers to MW in lesions in patients with MS. RESULTS: Both simulation and phantom studies showed that when TR was sufficiently short (e.g., 250 ms), the STAIR sequence effectively suppressed long T(1) signals from tissues with a broad range of T(1)s using a single TR/TI combination. The volunteer study showed a short T(2)* of 9.5±1.7ms in WM which is similar to reported values for MW. Lesions in MS patients showed a significantly lower aMWF (4.5±1.0%) compared with that of NWM (9.2±1.5%) in healthy volunteers (P

Magnetic resonance imaging (MRI) uses a large magnetic field and radio waves to generate images of tissues in the body. Conventional MRI techniques have been developed to image and quantify tissues and fluids with long transverse relaxation times (T2s), such as muscle, cartilage, liver, white matter, gray matter, spinal cord, and cerebrospinal fluid. However, the body also contains many tissues and tissue components such as the osteochondral junction, menisci, ligaments, tendons, bone, lung parenchyma, and myelin, which have short or ultrashort T2s. After radio frequency excitation, their transverse magnetizations typically decay to zero or near zero before the receiving mode is enabled for spatial encoding with conventional MR imaging. As a result, these tissues appear dark, and their MR properties are inaccessible. However, when ultrashort echo times (UTEs) are used, signals can be detected from these tissues before they decay to zero. This review summarizes recent technical developments in UTE MRI of tissues with short and ultrashort T2 relaxation times. A series of UTE MRI techniques for high-resolution morphological and quantitative imaging of these short-T2 tissues are discussed. Applications of UTE imaging in the musculoskeletal, nervous, respiratory, gastrointestinal, and cardiovascular systems of the body are included.

PURPOSE We describe the measurement of bound water T1 ( T1BW ) of cortical bone in vitro and in vivo with a 3D adiabatic inversion recovery ultrashort echo time (IR-UTE) Cones sequence using a clinical 3T scanner. METHODS A series IR-UTE data from 6 repetition times (TRs) with 5 inversion times (TIs) at each TR were acquired from 12 human tibial bone specimens, and data from 4 TRs with 5 TIs at each TR were acquired from the tibial midshafts of 8 healthy volunteers. The pore water nulling point was calculated from exponential fitting of the inversion recovery curve at each TR. Bone specimens and volunteers were then scanned again with the calculated nulling point at each TR. T1BW was derived through exponential fitting of data from IR-UTE images acquired at different TRs using the calculated pore water nulling point for each TR. RESULTS In vitro pore water nulling TIs were 141.3 ± 11.6, 123.4 ± 8.9, 101.3 ± 6.2, 88.9 ± 5.3, 74.8 ± 4.2, and 59.2 ± 3.9 ms for the 6 TRs of 500, 400, 300, 250, 200, and 150 ms, respectively. In vivo pore water nulling TIs were 132.8 ± 12.8, 110.3 ± 10.0, 80.0 ± 7.2, and 63.9 ± 5.4 ms for the 4 TRs of 400, 300, 200, and 150 ms, respectively. Excellent exponential fitting was achieved for IR-UTE imaging of bound water with pore water nulled at each TR. The mean T1BW was 106.9 ± 6.3 ms in vitro and 112.3 ± 16.4 ms in vivo. CONCLUSION Using the 3D IR-UTE Cones with a variable TR/TI approach, T1BW of cortical bone was calculated after complete nulling of pore water signals.

Long T2 water contamination is a major challenge with direct in vivo UTE imaging of ultrashort T2 components in the brain since water contributes most of the signal detected from white and gray matter. The Short TR Adiabatic Inversion Recovery prepared Ultrashort TE (STAIR-UTE) sequence can significantly suppress water signals and simultaneously image ultrashort T2 components. However, the TR used may not be sufficiently short to allow the STAIR preparation to completely suppress all the water signals in the brain due to specific absorption rate (SAR) limitations on clinical MR scanners. In this study, we describe a STAIR prepared dual-echo UTE sequence with complex Echo Subtraction (STAIR-dUTE-ES) which improves water suppression for selective ultrashort T2 imaging compared with that achieved with the STAIR-UTE sequence. Numerical simulations showed that the STAIR-dUTE-ES technique can effectively suppress water signals and allow accurate quantification of ultrashort T2 protons. Volunteer and Multiple Sclerosis (MS) patient studies demonstrated the feasibility of the STAIR-dUTE-ES technique for selective imaging and quantification of ultrashort T2 components in vivo. A significantly lower mean UltraShort T2 Proton Fraction (USPF) was found in lesions in MS patients (5.7±0.7%) compared with that in normal white matter of healthy volunteers (8.9±0.6%). The STAIR-dUTE-ES sequence provides robust water suppression for volumetric imaging and quantitation of ultrashort T2 component. The reduced USPF in MS lesions shows the clinical potential of the sequence for diagnosis and monitoring treatment in MS.

This paper reviews magnetic resonance (MR) pulse sequences in which the same or different tissue properties (TPs) such as T(1) and T(2) are used to contribute synergistically to lesion contrast. It also shows how synergistic contrast can be created with Multiplied, Added, Subtracted and/or fiTted Inversion Recovery (MASTIR) sequences, and be used to improve the sensitivity, specificity and scope of clinical magnetic resonance imaging (MRI) protocols. Synergistic contrast can be created from: (i) the same TP, e.g., T(1) used twice or more in a pulse sequence; (ii) different TPs such as ρ(m), T(1), T(2), and D* used once or more within a sequence, and (iii) additional suppression or reduction of signals from tissues and/or fluids such as fat, long T(2) tissues and cerebrospinal fluid (CSF). The short inversion time (TI) inversion recovery (IR) (STIR) and double IR (DIR) sequences usually show synergistic positive contrast for lesions which have increases in both T(1) and T(2). The diffusion weighted pulsed gradient spin echo (PGSE) sequence shows synergistic contrast for lesions which have an increase in T(2) and a decrease in D*; the sequence is both positively weighted for T(2) and negatively weighted for D*. In the brain, when an IR sequence nulling white matter has subtracted from it an IR sequence nulling gray matter to form the subtracted IR (SIR) sequence, increases in the single TP T(1) between the two nulling points of the original two sequences generate high synergistic positive contrast. In addition, the subtraction to produce the SIR sequence reduces fat and CSF signals. To provide high sensitivity to changes in TPs in disease the SIR sequence can be used (i) alone to provide synergistic T(1) contrast as above; (ii) with T(2)-weighting to provide synergistic T(1) and T(2) contrast, and (iii) with T(2)- and D*-weighting to provide synergistic T(1), T(2), and D* contrast. The SIR sequence can also be used in reversed form (longer TI form minus shorter TI form) to produce very high positive synergistic T(1) contrast for reductions in T(1), and so increase the positive contrast enhancement produced by clinical gadolinium-based contrast agents (GBCAs) when they reduce T(1). The specificity of MRI examinations can be improved by using the reversed SIR sequence with a long echo time (TE) gradient echo as well as echo subtraction to show synergistic high contrast from T(1) and T(2)* shortening produced by organic iron. Other added and subtracted forms of the MASTIR sequence can be used synergistically to selectively show myelin, myelin water and fluids including blood and CSF. Protocols using MASTIR sequences to provide synergistic contrast in MRI of the brain, prostate and articular cartilage are included as illustrative examples, and the features of synergistic contrast MRI (scMRI) are compared to those of multiparametric MRI (mpMRI) and functional MRI (fMRI).

PURPOSE: To describe a new method for accurate T(1) measurement of cortical bone which fits the datasets of both 3D UTE Actual Flip Angle Imaging (UTE-AFI) and UTE with a Single TR (UTE-STR) simultaneously (UTE-AFI-STR). THEORY AND METHODS: To make both the constant values and longitudinal mapping functions in the signal equations for UTE-AFI and UTE-STR identical, the same RF pulses and flip angles were used. Therefore, there were three unknowns in the three equations. This was sufficient to fit the data. Numerical simulation as well as ex vivo and in vivo cortical bone studies were performed to validate the T(1) measurement accuracy with the UTE-AFI-STR method. The original UTE-AFI-VTR (i.e. combined UTE-AFI and UTE with Variable TR (UTE-VTR)) and simultaneous fitting (sf) of UTE-AFI and UTE-VTR (sf-UTE-AFI-VTR) methods were performed for comparison. RESULTS: The numerical simulation study showed that the UTE-AFI-STR method provided accurate value of T(1) when the SNR of the UTE-STR image was higher than 40. The ex vivo study showed that the UTE-AFI-STR method measured the T(1) of cortical bone accurately, with difference ratios ranging from −5.0% to 0.4%. In vivo study showed a mean T(1) of 246 ms with the UTE-AFI-STR method, and mean difference ratios of 2.4% and 5.0% respectively compared with the other two methods. CONCLUSION: The 3D UTE-AFI-STR method provides accurate mapping of the T(1) of cortical bone with improved time efficiency compared with the UTE-AFI-VTR/sf-UTE-AFI-VTR methods.

BACKGROUND AND PURPOSE: MR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS. MATERIALS AND METHODS: The 2D inversion recovery ultrashort TE sequence was evaluated in 14 healthy volunteers and 31 patients with MS. MPRAGE and T2-FLAIR images were acquired for comparison. Advanced Normalization Tools were used to correlate inversion recovery ultrashort TE, MPRAGE, and T2-FLAIR images with disability assessed by the Expanded Disability Status Scale. RESULTS: Weak correlations were observed between normal-appearing white matter volume (R = –0.03, P = .88), lesion load (R = 0.22, P = .24), and age (R = 0.14, P = .44), and disability. The MPRAGE signal in normal-appearing white matter showed a weak correlation with age (R = –0.10, P = .49) and disability (R = –0.19, P = .31). The T2-FLAIR signal in normal-appearing white matter showed a weak correlation with age (R = 0.01, P = .93) and disability (R = 0.13, P = .49). The inversion recovery ultrashort TE signal was significantly negatively correlated with age (R = –0.38, P = .009) and disability (R = –0.44; P = .01). CONCLUSIONS: Direct imaging of myelin correlates with disability in patients with MS better than indirect imaging of long-T2 water in WM using conventional clinical sequences.

Author(s): Ma, Ya-Jun; Lu, Xing; Carl, Michael; Zhu, Yanchun; Szeverenyi, Nikolaus M; Bydder, Graeme M; Chang, Eric Y; Du, Jiang | Abstract: PurposeTo develop an accurate T1 measurement method for short T2 tissues using a combination of a 3-dimensional ultrashort echo time cones actual flip angle imaging technique and a variable repetition time technique (3D UTE-Cones AFI-VTR) on a clinical 3T scanner.MethodsFirst, the longitudinal magnetization mapping function of the excitation pulse was obtained with the 3D UTE-Cones AFI method, which provided information about excitation efficiency and B1 inhomogeneity. Then, the derived mapping function was substituted into the VTR fitting to generate accurate T1 maps. Numerical simulation and phantom studies were carried out to compare the AFI-VTR method with a B1 -uncorrected VTR method, a B1 -uncorrected variable flip angle (VFA) method, and a B1 -corrected VFA method. Finally, the 3D UTE-Cones AFI-VTR method was applied to bovine bone samples (N = 6) and healthy volunteers (N = 3) to quantify the T1 of cortical bone.ResultsNumerical simulation and phantom studies showed that the 3D UTE-Cones AFI-VTR technique provides more accurate measurement of the T1 of short T2 tissues than the B1 -uncorrected VTR and VFA methods or the B1 -corrected VFA method. The proposed 3D UTE-Cones AFI-VTR method showed a mean T1 of 240 ± 25 ms for bovine cortical bone and 218 ± 10 ms for the tibial midshaft of human volunteers, respectively, at 3 T.ConclusionThe 3D UTE-Cones AFI-VTR method can provide accurate T1 measurements of short T2 tissues such as cortical bone. Magn Reson Med 80:598-608, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Ultrashort TE (UTE) sequences have the capability to image tissues with very short T2s that typically appear as low signal in clinical sequences. UTE sequences can also be used in multi-echo acquisitions which allow assessment of the T2s of these tissues. Here we study the accuracy of such T2 measurements when combined with fat saturation (FS).

In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2 water protons. Magnitude and phase imaging and T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D 2 O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ~ 300 μs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from − 7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTE sequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.

Multiple sclerosis (MS)causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (less than 1 ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3T scanner. The technique was first validated on a synthetic myelinphantom (myelin powder in D2O) and a Feridex iron phantom. This was followed by studies of cadaveric MS specimens, healthy volunteers and MS patients. UTE imaging of the synthetic myelin phantom showed an excellent bi-component signal decay with two populations of protons, one with a T2* of 1.2 ms (residual water protons) and the other with a T2* of 290 μs (myelin protons). IR-UTE imaging shows sensitivity to a wide range of iron concentrations from 0.5 to ∼30 mM. The IR-UTE signal from white matter of the brain of healthy volunteers shows a rapid signal decay with a short T2* of ∼300 μs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter.

PURPOSE: We describe the measurement of bound water T(1) (T(1)(BW)) of cortical bone in vitro and in vivo with a 3D adiabatic inversion recovery ultrashort echo time (IR-UTE) Cones sequence using a clinical 3T scanner. METHODS: A series IR-UTE data from six repetition times (TRs) with five inversion times (TIs) at each TR were acquired from 12 human tibial bone specimens, and data from four TRs with five TIs at each TR were acquired from the tibial midshafts of eight healthy volunteers. The pore water nulling point was calculated from exponential fitting of the inversion recovery curve at each TR. Bone specimens and volunteers were then scanned again with the calculated nulling point at each TR. T(1)(BW) was derived through exponential fitting of data from IR-UTE images acquired at different TRs using the calculated pore water nulling point for each TR. RESULTS: In vitro pore water nulling TIs were 141.3±11.6, 123.4±8.9, 101.3±6.2, 88.9±5.3, 74.8±4.2, and 59.2±3.9 ms for the six TRs of 500, 400, 300, 250, 200 and 150ms, respectively. In vivo pore water nulling TIs were 132.8±12.8, 110.3±10.0, 80.0±7.2, and 63.9±5.4 ms for the four TRs of 400, 300, 200 and 150 ms, respectively. Excellent exponential fitting was achieved for IR-UTE imaging of bound water with pore water nulled at each TR. The mean T(1)(BW) was 106.9±6.3 ms in vitro and 112.3±16.4 ms in vivo. CONCLUSION: Using the 3D IR-UTE Cones with a variable TR/TI approach, T(1)(BW) of cortical bone was calculated after complete nulling of pore water signals.

Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR- UTE sequences at different TEs. T2* values of ~110–330 μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS.

Purpose To determine the relationship between lamellar layer thickness on ultrashort echo time (UTE) magnetic resonance (MR) images and indentation stiffness of human menisci and to compare quantitative MR imaging values between two groups with normal and abnormally thick lamellar layers. Materials and Methods This was a HIPAA-compliant, institutional review board-approved study. Nine meniscal pieces were obtained from seven donors without gross meniscal pathologic results (mean age, 57.4 years ± 14.5 [standard deviation]). UTE MR imaging and T2, UTE T2*, and UTE T1ρ mapping were performed. The presence of abnormal lamellar layer thickening was determined and thicknesses were measured. Indentation testing was performed. Correlation between the thickness and indentation stiffness was assessed, and mean quantitative MR imaging values were compared between the groups. Results Thirteen normal lamellar layers had mean thickness of 232 μm ± 85 and indentation peak force of 1.37 g ± 0.87. Four abnormally thick lamellar layers showed mean thickness of 353.14 μm ± 98.36 and peak force 0.72 g ± 0.31. In most cases, normal thicknesses showed highly positive correlation with the indentation peak force (r = 0.493-0.912; P < .001 to .05). However, the thickness in two abnormal lamellar layers showed highly negative correlation (r = -0.90, P < .001; and r = -0.23, P = .042) and no significant correlation in the others. T2, UTE T2*, and UTE T1ρ values in abnormally thick lamellar layers were increased compared with values in normal lamellar layers, although only the UTE T2* value showed significant difference (P = .010). Conclusion Variation of lamellar layer thickness in normal human menisci was evident on two-dimensional UTE images. In normal lamellar layers, thickness is highly and positively correlated with surface indentation stiffness. UTE T2* values may be used to differentiate between normal and abnormally thickened lamellar layers. (©) RSNA, 2016.

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T2 ), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three-dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T2 *, T1 , and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in 'free' form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort-TE (UTE) MRI techniques for the assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3-T clinical whole-body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO-H2O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro-computed tomography (μCT). A short T2* of 0.27 ± 0.03 ms and T1 of 116 ± 6 ms were observed for collagen-bound water in bovine bone. A longer T2* of 1.84 ± 0.52 ms and T1 of 527 ± 28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7-5.3% by volume and collagen-bound water concentration of 15.7-17.9% in bovine bone. THO-H2O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen-bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetric analysis showed a pore water concentration of 6.3 ± 0.8% and collagen-bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO-H2O exchange study. UTE-measured pore water concentration is highly correlated (R(2) = 0.72, p

Author(s): Carl, Michael; Bydder, Graeme M; Du, Jiang | Abstract: PurposeThe long repetition time and inversion time with inversion recovery preparation ultrashort echo time (UTE) often causes prohibitively long scan times. We present an optimized method for long T2 signal suppression in which several k-space spokes are acquired after each inversion preparation.Theory and methodsUsing Bloch equations the sequence parameters such as TI and flip angle were optimized to suppress the long T2 water and fat signals and to maximize short T2 contrast. Volunteer imaging was performed on a healthy male volunteer. Inversion recovery preparation was performed using a Silver-Hoult adiabatic inversion pulse together with a three-dimensional (3D) UTE (3D Cones) acquisition.ResultsThe theoretical signal curves generally agreed with the experimentally measured region of interest curves. The multispoke inversion recovery method showed good muscle and fatty bone marrow suppression, and highlighted short T2 signals such as these from the femoral and tibial cortex.ConclusionInversion recovery 3D UTE imaging with multiple spoke acquisitions can be used to effectively suppress long T2 signals and highlight short T2 signals within clinical scan times. Theoretical modeling can be used to determine sequence parameters to optimize long T2 signal suppression and maximize short T2 signals. Experimental results on a volunteer confirmed the theoretical predictions. Magn Reson Med 76:577-582, 2016. © 2015 Wiley Periodicals, Inc.

PURPOSE: Ultrashort echo time (UTE) sequences with a minimal nominal TE of 8 µs have shown promise for direct imaging of myelin protons (T(2), < 1 ms). However, there is still debate about the efficiency of 2D slice-selective UTE sequences in exciting myelin protons because the half excitation pulses used in these sequences have a relatively long duration (e.g., 0.3-0.6 ms). Here we compared UTE and inversion-recovery UTE (IR-UTE) sequences used with either hard or half excitation pulses (durations 32 µs or 472 µs, respectively) for imaging myelin in native and deuterated ovine brain at 3T. METHODS: Freshly-frozen ovine brains were dissected into ~2 mm thick pure white matter and ~3-8 mm thick cerebral hemisphere specimens, which were imaged before and/or after different immersion time in D(2)O. RESULTS: Bi-component T(2)* analysis of UTE signals obtained with hard excitation pulses detected an ultrashort T(2) component (STC) fraction (f(S)) of 0-10% in native specimens, and up to ~86% in heavily deuterated specimens. f(S) values were significantly affected by the TIs used in IR-UTE sequences with either hard or half excitation pulses in native specimens, but not in heavily deuterated specimens. The STC T(2)*s were in the range of 150-400 µs in all UTE and IR-UTE measurements obtained with either hard or half excitation pulses. CONCLUSION: Our results further support myelin protons as the major source of the ultrashort T(2)* signals seen on IR-UTE images, and demonstrate the potential of IR-UTE sequences with half excitation pulses for directly imaging myelin using clinical scanners.

To determine the feasibility of using MR microscopy to characterize the root ligaments of the human knee at both ultra-high-field (11.7 T) and high-field (3 T) strengths. Seven fresh cadaveric knees were used for this study. Six specimens were imaged at 11.7 T and one specimen at 3 T using isotropic or near-isotropic voxels. Histologic correlation was performed on the posteromedial root ligament of one specimen. Meniscal root ligament shape, signal intensity, and ultrastructure were characterized. High-resolution, high-contrast volumetric images were generated from both MR systems. Meniscal root ligaments were predominantly oval in shape. Increased signal intensity was most evident at the posteromedial and posterolateral root ligaments. On the specimen that underwent histologic preparation, increased signal intensity corresponded to regions of enthesis fibrocartilage. Collagen fascicles were continuous between the menisci and root ligaments. Predominantly horizontal meniscal radial tie fibers continued into the root ligaments as vertical endoligaments. MR microscopy can be used to characterize and delineate the distinct ultrastructure of the root ligaments on both ultra-high-field- and high-field-strength MR systems.

The purpose of this study is to develop a 3D adiabatic inversion recovery prepared ultrashort echo time Cones (3D IR-UTE-Cones) sequence for high resolution and contrast imaging of the region of osteochondral junction (OCJ) of human knee joint using a clinical 3 T scanner. A feasibility study on direct imaging of the OCJ region was performed on a human patellar cartilage sample and on eight cadaveric knee joints using T1 -weighted, proton density (PD)-weighted and short-T2 -weighted 3D IR-UTE-Cones sequences. Contrast to noise ratio was measured to evaluate the effectiveness of the 3D IR-UTE-Cones sequences for selective imaging of the OCJ region. Computed tomography imaging was performed in parallel for the cadaveric knee joints. The optimized T1 -weighted 3D IR-UTE-Cones sequence was used to image the knee joints of eight healthy volunteers and six patients with osteoarthritis (OA) to evaluate morphological changes in the OCJ region. Clinical PD- and T2 -weighted FSE sequences were also performed for comparison. The T1 -weighted 3D IR-UTE-Cones sequence showed high resolution and contrast bright band of the normal OCJ region in the cadaveric joints. Normal OCJ appearances were also seen in healthy volunteers. Abnormal OCJ regions, manifested as ill-defined, focal loss or non-visualization of the high intensity band adjacent to the subchondral bone plate, were observed in the knee joints of both ex vivo and in vivo OA patients. The 3D IR-UTE-Cones sequence can image OCJ regions ex vivo and in vivo, with abnormalities depicted with high resolution and contrast. The technique may be useful for demonstrating involvement of OCJ regions in early OA.

Most of the currently available clinical and research magnetic resonance imaging techniques have focused on the more superficial layers of articular cartilage. This has mainly been because the study of early and late alterations to the deeper layers of cartilage, including the deep radial zone and calcified cartilage, has not been possible due to the technical limitations of clinical scanners. In recent years, several types of two- and three-dimensional ultrashort echo time (UTE) sequences have been developed for high-resolution morphological imaging of articular cartilage. Various contrast mechanisms have been used to image the different layers of articular cartilage, especially calcified cartilage. Quantitative UTE imaging sequences have also been developed to measure T1, T1ρ and T2* in the different layers of articular cartilage. Both bound and bulk water components, including their T2*s and relative fractions, can also be assessed using UTE sequences based on multi-component analysis of UTE signal decay.

Osteoporosis causes over 1.5 million fractures per year, costing about $15 billion annually in the USA. Current guidelines utilize bone mineral density (BMD) to assess fracture risk; however, BMD alone only accounts for 30-50% of fractures. The other two major components of bone, organic matrix and water, contribute significantly to bone mechanical properties, but cannot be assessed with conventional imaging techniques in spite of the fact that they make up about 57% of cortical bone by volume. Conventional clinical MRI usually detects signals from water in tissues without difficulty, but cannot detect the water bound to the organic matrix, or the free water in the microscopic pores of the Haversian and the lacunar-canalicular system of cortical bone, because of their very short apparent transverse relaxation times (T2 *). In recent years, a new class of sequences, ultrashort-TE (UTE) sequences, with nominal TEs of less than 100 µs, which are much shorter than the TEs available with conventional sequences, have received increasing interest. These sequences can detect water signals from within cortical bone and provide an opportunity to study disease of this tissue in a new way. This review summarizes the recent developments in qualitative UTE imaging (techniques and contrast mechanisms to produce bone images with high contrast) and quantitative UTE imaging (techniques to quantify the MR properties, including T1 , T2 * and the magnetization transfer ratio, and tissue properties, including bone perfusion, as well as total, bound and free water content) of cortical bone in vitro and in vivo. The limitations of the current techniques for clinical applications and future directions are also discussed.

We describe the use of ultrashort echo time (UTE) sequences and fast spin echo sequences to assess cortical bone using a clinical 3T scanner. Regular two- and three-dimensional UTE sequences were used to image both bound and free water in cortical bone. Adiabatic inversion recovery prepared UTE sequences were used to image water bound to the organic matrix. Two-dimensional fast spin echo sequences were used to image free water. Regular UTE sequences were used together with bicomponent analysis to measure T*2s and relative fractions of bound and free water components in cortical bone. Inversion recovery prepared UTE sequences were used to measure the T*2 of bound water. Saturation recovery UTE sequences were used to measure the T1 of bone water. Eight cadaveric human cortical bone samples and a lower leg specimen were studied. Preliminary results show two distinct components in UTE detected signal decay, a single component in inversion recovery prepared UTE detected signal decay, and a single component in saturation recovery UTE detected signal recovery. Regular UTE sequences appear to depict both bound and free water in cortical bone. Inversion recovery prepared UTE sequences appear to depict water bound to the organic matrix. Two-dimensional fast spin echo sequences appear to depict bone structure corresponding to free water in large pores.

To correlate short and long T2* water fractions, derived from ultrashort-echo time (TE) magnetic resonance (MR) imaging, with semiquantitative histopathologic and polarized light microscopic (PLM) assessment of human cadaveric patellae cartilage.Twenty human cadaveric patellae were evaluated by using ultrashort-TE imaging, spin-echo imaging, histopathologic analysis, and PLM, with institutional review board approval. Short and long T2* water components were evaluated for each patella by using bicomponent fitting of ultrashort-TE signal decay. Four to six regions of interest (ROIs) within each patella were chosen for correlation between ultrashort-TE bicomponent analysis, histopathologic grading (Mankin score), and PLM grading (Vaudey score).Ultrashort-TE imaging with bicomponent analysis showed two distinct water components with a short T2* and a longer T2* in all patellae. ROI analysis showed that the short T2* fraction was correlated significantly with the Mankin (ρ = 0.66, P.001) and Vaudey (ρ = 0.68, P.001) scores. The Mankin scores were weakly positively correlated with T2 (ρ = 0.28, P = .13) and short T2* (ρ = 0.24, P = .14) but were negatively correlated with long T2* (ρ = -0.55, P.01). The Vaudey scores were weakly positively correlated with T2 (ρ = 0.18, P = .16) and short T2* (ρ = 0.22, P = .14) but were negatively correlated with long T2* (ρ = -0.55, P.01).Short T2* water fraction derived from ultrashort-TE imaging with bicomponent analysis correlates significantly with both the Mankin and Vaudey scores and may serve as a biomarker of cartilage degeneration.

PURPOSE: To assess the ability of ultrashort echo time (UTE) magnetic resonance (MR) imaging techniques to enable morphologic assessment of different types of meniscal calcifications, to compare these sequences with standard clinical sequences, and to perform T2* measurements of meniscal calcifications. MATERIALS AND METHODS: This study was exempted by the institutional review board, and informed consent was not required. Ten human cadaveric menisci were imaged with high-spatial-resolution radiography and 3.0-T MR imaging by using morphologic (T1-weighted fast spin-echo [FSE], T2-weighted FSE, proton density [PD]-weighted FSE, two-dimensional [2D] fast spoiled gradient-echo [FSPGR], three-dimensional [3D] FSPGR, and 3D UTE) and quantitative (2D inversion-recovery [IR] UTE and 3D UTE) sequences. The menisci were divided into thirds for regional analysis. Morphologic assessment was performed with MR imaging; MR imaging findings were correlated with radiographs. Calcifications were classified as punctate, linear, or globular. T2* measurements were performed by manual placement of regions of interest (ROIs) in calcifications and by automatically creating ROIs in the surrounding tissues. Mixed-effects linear regression was used to determine variations in T2* as a function of region, morphology, and tissue type. RESULTS: The two globular calcifications were visualized with all sequences. For punctate (n=21) and linear (n=21) calcifications, respectively, visibility rates were as follows: 9.5% for both with the T1-weighted FSE sequence, 0% for both with the T2-weighted FSE sequence, 19.0% and 23.8% with the PD-weighted FSE sequence, 0% for both with the 2D IR UTE sequence, 100% for both with the 3D UTE sequence, and 100% for both with the 3D FSPGR sequence. T2* values were significantly lower for calcifications than for the surrounding meniscal tissue (P

An ultrashort TE T(1)ρ sequence was used to measure T(1) ρ of the goat posterior cruciate ligament (n = 1) and human Achilles tendon specimens (n = 6) at a series of angles relative to the B(0) field and spin-lock field strengths to investigate the contribution of dipole-dipole interaction to T(1)ρ relaxation. Preliminary results showed a significant magic angle effect. T(1)ρ of the posterior cruciate ligament increased from 6.9 ± 1.3 ms at 0° to 36 ± 5 ms at 55° and then gradually reduced to 12 ± 3 ms at 90°. Mean T(1)ρ of the Achilles tendon increased from 5.5 ± 2.2 ms at 0° to 40 ± 5 ms at 55°. T(1)ρ dispersion study showed a significant T(1)ρ increase from 2.3 ± 0.9 ms to 11 ± 3 ms at 0° as the spin-lock field strength increased from 150 Hz to 1 kHz, and from 30 ± 3 ms to 42 ± 4 ms at 55° as the spin-lock field strength increased from 100 to 500 Hz. These results suggest that dipolar interaction is the dominant T(1)ρ relaxation mechanism in tendons and ligaments.

Recent proton magnetic resonance (MR) spectroscopy studies have shown that cortical bone exists as different components which have distinct transverse relaxation times (T2s). However, cortical bone shows zero or near zero signal with all conventional MR sequences on clinical scanners and the different water components cannot be assessed with this approach. In order to detect signal in this situation a two-dimensional (2D) non-slice selective ultrashort echo time (UTE) pulse sequence with a nominal TE of 8 μs was used together with bi-component analysis to quantify bound and free water in bovine cortical bone at 3T. Total water concentration was quantified using a 3D UTE sequence together with a reference water phantom. 2D and 3D UTE imaging were performed on 14 bovine bone samples which were subjected to sequential air-drying to evaluate free water loss, followed by oven-drying to evaluate bound water loss. Sequential bone weight loss was measured concurrently using a precision balance. Bone porosity was measured with micro computed tomography (μCT) imaging. UTE measured free water loss was higher than the volume of cortical pores measured with μCT, but lower than the gravimetric bone water loss measured during air-drying. UTE assessed bound water loss was about 82% of gravimetric bone water loss during oven-drying. On average bovine cortical bone showed about 13% free water and 87% bound water. There was a high correlation (R = 0.91; P < 0.0001) between UTE MR measured free water loss and gravimetric bone weight loss during sequential air-drying, and a significant correlation (R = 0.69; P < 0.01) between UTE bound water loss and gravimetric bone weight loss during oven-drying. These results show that UTE bi-component analysis can reliably quantify bound and free water in cortical bone. The technique has potential applications for the in vivo evaluation of bone porosity and organic matrix.

A variety of techniques are now available to directly or indirectly detect signal from tissues, fluids and materials that have short, ultrashort or supershort T2 or T2* components. There are also methods of developing image contrast between tissues and fluids in the short T2 or T2* range that can provide visualisation of anatomy, which has not been previously seen with MRI. Magnetisation transfer methods can now be applied to previously invisible tissues, providing indirect access to supershort T2 components. Particular methods have been developed to target susceptibility effects and quantify them after correcting for anatomical distortion. Specific methods have also been developed to image the effects of magnetic iron oxide particles with positive contrast. Major advances have been made in techniques designed to correct for loss of signal and gross image distortion near metal. These methods are likely to substantially increase the range of application for MRI.

The effects of water loss on the T1 and T2* of bovine cortical bone were investigated using ultrashort echo time sequences with signals excited either by a short hard pulse or by two longer half pulses. Nine bovine femur samples were prepared and sequentially air- and oven-dried. On average 3.42% of bone by weight was lost after air-drying for 3 days, with another 5.98% of bone weight loss after oven-drying at 100°C for 24 h. T1 and T2* were measured after every 1% decrease in weight, with 9-10% bone weight loss at the termination of the drying process. After both forms of drying, the overall T1 decreased 33% from 153±18 ms to 102±17 ms when measured using the hard pulse and from 186±25 ms to 122±23 ms when using the half pulses. T2* decreased by 45-50% from 368±29 μs to 201±19 μs using the hard pulse and from 379±35 μs to 191±17 μs using the half pulses. A steady decrease of 26-31% was observed in both T1 and T2* with the first 3-4% bone water loss after air-drying. Oven-drying at 100°C for 24 h resulted on an additional 4% T1 reduction but 25% T2* reduction.

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T(1) shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T(2)*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T(1) and T(2)* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T(1) contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T(2)* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T(1) and T(2)* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo.

Carotid plaque calcification normally appears as a signal void with clinical MR sequences. Here, we describe the use of an adiabatic inversion recovery prepared two-dimensional ultrashort echo time sequence to image and characterize carotid plaque calcification using a clinical 3-T scanner. T1, T, and free water content were measured for seven carotid samples, and the results were compared with micro-CT imaging. Conventional gradient echo and fast spin echo images were also acquired for comparison. Correlations between T1, T, free water concentration, and mineral density were performed. There was a close correspondence between inversion recovery prepared two-dimensional ultrashort echo time morphologic and micro-CT appearances. Carotid plaque calcification varied significantly from sample to sample, with T1s ranging from 94 ± 19 to 328 ± 21 msec, Ts ranging from 0.31 ± 0.12 to 2.15 ± 0.25 msec, and free water concentration ranging from 5.7 ± 2.3% to 16.8 ± 3.4%. There was a significant positive correlation between T1 (R = 0.709; P < 0.074), T (R = 0.816; P < 0.025), and free water concentration, a negative correlation between T1 (R = 0.773; P < 0.042), T (R = 0.948; P < 0.001) and CT measured mineral density, and a negative correlation between free water concentration (R = 0.936; P < 0.002) and mineral density. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.

Magnetic resonance imaging (MRI) examination of musculoskeletal tissues is being performed routinely for diagnoses of injury and diseases. Although conventional MRI using spin echo sequences has been effective, a number of important musculoskeletal soft tissues remain "magnetic resonance-invisible" because of their intrinsically short T2 values resulting in a rapid signal decay. This makes visualization and quantitative characterization difficult. With the advent and refinement of ultrashort time-to-echo (UTE) MRI techniques, it is now possible to directly visualize and quantitatively characterize these tissues. This review explores the anatomy, conventional MRI, and UTE MRI of articular cartilage, meniscus of the knee, and intervertebral disks and provides a survey of magnetic resonance studies used to better understand tissue structure, composition, and function, as well as subtle changes in diseases.

Purpose: Four devices are described as variants of a single concept to assist the imaging of tissues with T2 relaxation times substantially influenced by dipolar coupling. The signal levels of such tissues are subjected to “magic angle” effects and determined by their orientation to B0. Methods: The pneumatically actuated devices remotely move patient's anatomy so that the angle of tissues relative to B0 can be easily adjusted within a closed-bore MRI scanner. Images taken with tissues at various orientations are analyzed to study the dipolar coupling effects. The devices include: a small hand unit, a unit for the Achilles tendon, a 3DOF platform for imaging the knee, and an upper limb unit. Results: Results obtained with all four devices are illustrated, demonstrating their utility to manipulate anatomy in an MRI environment. Conclusion: The successful demonstration of the devices can facilitate a fuller clinical evaluation of magic angle-related phenomena. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 37B: 220–225, 2010.

In this study, we report the use of a novel ultrashort echo time T(1)rhoT(1) sequence that combines a spin-lock preparation pulse with a two-dimensional ultrashort echo time sequence of a nominal echo time 8 microsec. The ultrashort echo time-T(1)rho sequence was employed to quantify T(1)rho in short T(2) tissues including the Achilles tendon and the meniscus. T(1)rho dispersion was investigated by varying the spin-lock field strength. Preliminary results on six cadaveric ankle specimens and five healthy volunteers show that the ultrashort echo time-T(1)rho sequence provides high signal and contrast for both the Achilles tendon and the meniscus. The mean T(1)rho of the Achilles tendon ranged from 3.06 +/- 0.51 msec for healthy volunteers to 5.22 +/- 0.58 msec for cadaveric specimens. T(1)rho increased to 8.99 +/- 0.24 msec in one specimen with tendon degeneration. A mean T(1)rho of 7.98 +/- 1.43 msec was observed in the meniscus of the healthy volunteers. There was significant T(1)rho dispersion in both the Achilles tendon and the meniscus. Mean T(1)rho increased from 2.06 +/- 0.23 to 7.85 +/- 0.74 msec in normal Achilles tendon and from 7.08 +/- 0.64 to 13.42 +/- 0.93 msec in normal meniscus when the spin-lock field was increased from 250 to 1,000 Hz.

There are now a variety of new techniques available to detect signal from tissues with short or ultrashort T2s and T2*s. There are also many methods of developing image contrast between tissues and fluids in the short T2 or T2* range, which can provide visualization of anatomy that has not previously been seen. Particular methods have been developed to target susceptibility effects, and allow accurate quantitation by compensating for the anatomical distortion produced by these effects. Specific methods have been developed to image the effects of magnetic iron oxide particles with positive contrast and to correct for the loss of signal and image distortion near to metal caused by gross susceptibility effects. These methods are likely to provide interesting options and increase the range of applications of MRI.

Imaging of short-T2 species requires not only a short echo time (TE) but also efficient suppression of long-T2 species in order to maximize the short-T2 contrast and dynamic range. This paper introduces a method of long-T2 suppression using two long adiabatic inversion pulses. The first adiabatic inversion pulse inverts the magnetization of long-T2 water and the second one inverts that of fat. Short-T2 species experience a significant transverse relaxation during the long adiabatic inversion process, and are minimally affected by the inversion pulses. Data acquisition with a short TE of 8 μs starts following a time delay of TI1 for the inverted water magnetization to reach a null point, and a time delay of TI2 for the inverted fat magnetization to reach a null point. The suppression of long-T2 species depends on proper combination of TI1, TI2 and TR. It is insensitive to RF inhomogeneities because of the adiabatic inversion pulses. The feasibility of this dual inversion recovery ultrashort TE (DIR UTE) technique was demonstrated on phantoms, cadaveric specimens and healthy volunteers using a clinical 3T scanner. High image contrast was achieved for the deep radial and calcified layers of articular cartilage, cortical bone and the Achilles tendon.

Short T(2) species such as the Achilles tendon and cortical bone cannot be imaged with conventional MR sequences. They have a much broader absorption lineshape than long T(2) species, therefore they are more sensitive to an appropriately placed off-resonance irradiation. In this work, a technique termed ultrashort TE (UTE) with off-resonance saturation contrast (UTE-OSC) is proposed to image short T(2) species. A high power saturation pulse was placed +1 to +2 kHz off the water peak to preferentially saturate signals from short T(2) species, leaving long T(2) water and fat signals largely unaffected. The subtraction of UTE images with and without an off-resonance saturation pulse effectively suppresses long T(2) water and fat signals, creating high contrast for short T(2) species. The UTE-OSC technique was validated on a phantom, and applied to bone samples and healthy volunteers on a clinical 3T scanner. High-contrast images of the Achilles tendon and cortical bone were generated with a high contrast-to-noise ratio (CNR) of the order of 12 to 20 between short T(2) and long T(2) species within a total scan time of 4 to 10 min.