In vivo evaluation of human patellar tendon microstructure and microcirculation with diffusion MRI.

BACKGROUND: Patellar tendon (PT) microstructure integrity and microcirculation status play a crucial role in the progression of tendinopathy and tendon repair. PURPOSE: To assess the feasibility and robustness of stimulated-echo based diffusion-weighted MRI with readout-segmented echo-planar imaging (ste-RS-EPI) for noninvasive assessment of microstructure and microcirculation of human PT. STUDY TYPE: Prospective. SUBJECTS: Fifteen healthy volunteers. FIELD STRENGTH/SEQUENCE: PT diffusion tensor imaging (DTI) and intravoxel incoherent motion (IVIM) were acquired with an ste-RS-EPI protocol on a 3T MRI scanner. ASSESSMENT: Subjects were positioned with their PT at the magic angle. DTI-derived parameters including axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) were estimated with b-values of 0 and 800 s/mm2 and 12 diffusion directions. IVIM-derived parameters, f p , D* × f p , V b , and D* × V b were assessed in the central-third and the outer-two thirds of the PT with b-values of 0, 20, 30, 60, 80, 120, 200, 400, and 600 s/mm2 in three orthogonal directions. STATISTICAL TESTS: Paired t-tests were used to evaluate differences in IVIM parameters between the central-third and outer-two thirds regions of the patellar tendon. Paired t-tests and within-subject coefficient of variation were used to assess the intra- and intersession reproducibility of PT DTI and IVIM parameters. RESULTS: DTI parameters for healthy PT were 1.54 ± 0.09 × 10-3 mm2 /s, 1.01 ± 0.05 × 10-3 mm2 /s, 1.18 ± 0.06 × 10-3 mm2 /s, and 0.30 ± 0.04 for AD, RD, MD, and FA, respectively. Significantly higher (P < 0.05) IVIM parameters f p and D* × f p were observed in the outer-two thirds (6.1% ± 2.4% and 95.2 ± 49.6, respectively) compared with the central-third (3.8% ± 2.3% and 48.6 ± 35.2, respectively) of the PT. DATA CONCLUSION: Diffusion MRI of PT with an ste-RS-EPI protocol is clinically feasible. Both DTI- and IVIM-derived parameters of the PT demonstrated good test-retest reproducibility and interrater reliability. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:780-790.

3D MRI of whole-brain water permeability with intrinsic diffusivity encoding of arterial labeled spin (IDEALS).

This work proposes a novel MRI method - Intrinsic Diffusivity Encoding of Arterial Labeled Spin (IDEALS) - for the whole-brain mapping of water permeability in the human brain without an exogenous contrast agent. Quantitative separation of the intravascular and extravascular labeled water MRI signal was achieved in arterial spin labeling experiments with segmented 3D-GRASE acquisition by modulating the relative sensitivity between relaxation, true diffusion, and pseudodiffusion. The intrinsic diffusivity encoding in k-space created different broadening of the image-domain point spread functions for intravascular and extravascular labeled spins, from which blood-brain barrier (BBB) water extraction fraction (Ew) and water permeability surface area product (PSw) were estimated. The feasibility and sensitivity of this method was evaluated in healthy subjects at baseline and after caffeine challenge. The estimated baseline Ew and PSw maps showed contrast among gray matter (GM) and white matter (WM). GM Ew was significantly lower than that of WM (78.8% ±â€¯3.3% in GM vs. 83.9% ±â€¯4.6% in WM; p < 0.05) and GM PSw was significantly higher than that of WM (131.7 ±â€¯29.5 mL/100  g/min in GM vs. 76.2 ±â€¯18.4 mL/100  g/min in WM; p < 0.05). BBB Ew was significantly lower for females than males (74.9% ±â€¯3.7% for females vs. 81.3% ±â€¯3.3% for males in GM; 80.5% ±â€¯4.7% for females vs. 86.1 ±â€¯3.0 for males in WM; p < 0.05 for both), while significant PSw differences were only observed in WM (143.8 ±â€¯34.4 mL/100  g/min for females vs. 123.6 ±â€¯24.4 mL/100  g/min for males in GM; 91.6 ±â€¯15.0 mL/100  g/min for females vs. 65.9 ±â€¯12.5 mL/100  g/min for males in WM; p = 0.20 and p < 0.05 for GM and WM respectively). Significant correlations between Ew and CBF (r = -0.32, p < 0.05) and between PSw and CBF (r = 0.89, p < 0.05) were observed, consistent with 15O-H2O PET findings. After caffeine challenge, reduced CBF, Ew and PSw were observed, demonstrating the sensitivity of IDEALS approach.

MRI biomarkers in osseous tumors.

Although radiography continues to play a critical role in osseous tumor assessment, there have been remarkable advances in cross-sectional imaging. MRI has taken a lead in this assessment due to high tissue contrast and spatial resolution, which are well suited for bone lesion assessment. More recently, although somewhat lagging other organ systems, quantitative parameters have shown promising potential as biomarkers for osseous tumors. Among these sequences are chemical shift imaging (CSI), apparent diffusion coefficient (ADC), and intravoxel incoherent motion (IVIM) from diffusion-weighted imaging (DWI), quantitative dynamic contrast enhanced (DCE)-MRI, and magnetic resonance spectroscopy (MRS). In this article, we review the background and recent roles of these quantitative MRI biomarkers for osseous tumors. Level of Evidence: 3 Technical Efficacy Stage: 3 J. MAGN. RESON. IMAGING 2019. J. Magn. Reson. Imaging 2019;50:702-718.

Abbreviated quantitative UTE imaging in anterior cruciate ligament reconstruction.

BACKGROUND: Existing ultrashort echo time magnetic resonance imaging (UTE MRI) methods require prohibitively long acquisition times (~ 20-40 min) to quantitatively assess the clinically relevant fast decay T2* component in ligaments and tendons. The purpose of this study was to evaluate the feasibility and clinical translatability of a novel abbreviated quantitative UTE MRI paradigm for monitoring graft remodeling after anterior cruciate ligament (ACL) reconstruction. METHODS: Eight patients who had Graftlink™ hamstring autograft reconstruction were recruited for this prospective study. A 3D double-echo UTE sequence at 3.0 Tesla was performed at 3- and 6-months post-surgery. An abbreviated UTE MRI paradigm was established based on numerical simulations and in vivo validation from healthy knees. This proposed approach was used to assess the T2* for fast decay component ([Formula: see text]) and bound water signal fraction (fbw) of ACL graft in regions of interest drawn by a radiologist. RESULTS: Compared to the conventional bi-exponential model, the abbreviated UTE MRI paradigm achieved low relative estimation bias for [Formula: see text] and fbw over a range of clinically relevant values for ACL grafts. A decrease in [Formula: see text] of the intra-articular graft was observed in 7 of the 8 ACL reconstruction patients from 3- to 6-months (- 0.11 ± 0.16 ms, P = 0.10). Increases in [Formula: see text] and fbw from 3- to 6-months were observed in the tibial intra-bone graft ([Formula: see text]: 0.19 ± 0.18 ms, P < 0.05; Δfbw: 4% ± 4%, P < 0.05). Lower [Formula: see text] (- 0.09 ± 0.11 ms, P < 0.05) was observed at 3-months when comparing the intra-bone graft to the graft/bone interface in the femoral tunnel. The same comparisons at the 6-months also yielded relatively lower [Formula: see text] (- 0.09 ± 0.12 ms, P < 0.05). CONCLUSION: The proposed abbreviated 3D UTE MRI paradigm is capable of assessing the ACL graft remodeling process in a clinically translatable acquisition time. Longitudinal changes in [Formula: see text] and fbw of the ACL graft were observed.

Correlation of bone marrow cellularity and metabolic activity in healthy volunteers with simultaneous PET/MR imaging.

OBJECTIVE: To evaluate the correlation between bone marrow cellularity (BMC) and metabolic activity in healthy subjects and to see whether yellow marrow is indeed metabolically quiescent. Because metabolic activity can be assumed to reflect vascularity, we assessed the relationship between regional metabolic activity and geographic frequency of metastases as noted in the literature. MATERIALS AND METHODS: Two hundred and twenty locations (ten in each side of the pelvis and proximal femur) were evaluated in 11 consecutive healthy volunteers with simultaneous PET/MR. BMC was calculated through precise water-fat fraction quantification with a 6-echo gradient echo. We analyzed correlations between cellularity and SUVr, age, and R2*. We also looked at the relation between our results and the reported prevalence of metastases. RESULTS: There was moderate but statistically significant correlation between BMC and metabolic activity (r = 0.636, p < 0.0001). Interestingly, the iliac and sacrum had higher metabolic activity relative to cellularity, whereas the femoral neck and lesser trochanter showed lower SUVr than other regions with the similar cellularity. The relatively lower metabolic status of the femoral neck conflicted with its reported high frequency of metastasis. Excluding regions with almost no remaining red marrow, cellularity showed inverse relationship with age (r = 0.476, p < 0.0001) and direct relationship with R2* (r = 0.532, p < 0.0010). CONCLUSIONS: Metabolic activity of bone marrow was largely dependent on BMC while yellow marrow seems metabolically quiescent. The discrepancy between the assumed vascularity as determined by metabolic activity and reported sites of metastasis suggested that the process of bone metastasis may not depend entirely on vascularity.

Diffusion sensitivity of 3D-GRASE in arterial spin labeling perfusion.

PURPOSE: To evaluate the role of true diffusion and flow-related pseudodiffusion in cerebral blood flow (CBF) quantification using arterial spin labeling (ASL) with single-shot or segmented 3D gradient and spin echo (GRASE) readouts. THEORY: The extended phase graph (EPG) algorithm, originally designed to model the effects of T1 /T2 relaxation and true diffusion in MRI acquisitions utilizing multiple refocusing RF pulses, was augmented (aEPG). This augmentation accounted for flow-related pseudodiffusion attenuation of intravascular MRI signal in the k-space domain during 3D-GRASE acquisition, which leads to blur along the partition direction in the image domain. Blurring of ASL signal into neighboring voxels can lead to underestimation of CBF in small, high-flow structures such as cortical gray matter (GM). METHODS: The diffusion sensitivity of 3D-GRASE was evaluated through aEPG simulations and in vivo experiments in 13 healthy subjects. The CBF estimation bias for different postlabeling delays, crusher gradient strengths, and segmentation factors along the partition (PAR) and phase-encoding (PE) directions was numerically assessed by simulations and experimentally validated. RESULTS: In vivo experiments demonstrated systematic underestimation of mean GM CBF measured with segmented 3D-GRASE. The GM CBF underestimation depended on ASL preparation and imaging parameters; it reached up to 25% at low-segmentation schemes (1PAR × 2PE ) but was considerably lower at high-segmentation schemes (4PAR × 2PE or 8PAR × 2PE ). Theoretical predictions showed that conventional T1 /T2 relaxation and true diffusion may account for at most ∼25% of GM CBF estimation bias, whereas the pseudodiffusion effect constituted the major fraction in a typical ASL experiment. CONCLUSION: The pseudodiffusion effect leads to considerable estimation bias in ASL-based CBF quantification using 3D-GRASE readouts. This bias can be substantially reduced by increasing the segmentation factors. Magn Reson Med 80:736-747, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Diffusion tensor imaging of human Achilles tendon by stimulated echo readout-segmented EPI (ste-RS-EPI).

PURPOSE: Healing, regeneration, and remodeling of the injured Achilles tendon are associated with notable changes in tendon architecture. However, assessing Achilles microstructural properties with conventional diffusion tension imaging (DTI) remains a challenge because of very short T2 / T 2 * values of the tendon. Hence, the objective of this study was to develop a novel Achilles tendon DTI protocol for a non-invasive investigation of the changes of microstructural integrity in tendinopathy. METHODS: A novel stimulated echo readout-segmented EPI (ste-RS-EPI) DTI sequence was proposed to achieve a TE of ∼14-20 ms for typical b-values of 400-800 s/mm2 on clinical 3T MRI scanners. To further boost tendon MR signal, the Achilles was positioned at the magic angle (∼55 °) with respect to the scanner B0 field. The sensitivity of the developed protocol was evaluated in 19 healthy participants and 6 patients with clinically confirmed tendinopathy. RESULTS: Compared to spin echo RS-EPI DTI protocol, ste-RS-EPI provided an ∼100-200% increase in Achilles MR signal. Tendinopathic Achilles demonstrated a high degree of microstructural disruption based on DTI tractography analysis, with significantly lower (P < 0.05) axial diffusivity (1.20 ± 0.19 vs. 1.39 ± 0.10 × 10-3 mm2 /s), radial diffusivity (0.72 ± 0.11 vs. 0.81 ± 0.08 × 10-3 mm2 /s), and mean diffusivity (0.87 ± 0.14 vs. 1.00 ± 0.07 × 10-3 mm2 /s), but no significant difference in fractional anisotropy (0.38 ± 0.04 vs. 0.38 ± 0.05; P = 0.86). CONCLUSION: Achilles tendon ste-RS-EPI DTI can non-invasively detect the tendinopathy-induced changes to microstructural integrity, consistent with the disruption of collagen arrangement and increased cellularity. This study demonstrated the robustness and sensitivity of the proposed protocol in Achilles tendinopathy.

Intravoxel incoherent motion (IVIM) imaging in human achilles tendon.

BACKGROUND: Limited microcirculation has been implicated in Achilles tendinopathy and may affect healing and disease progression. Existing invasive and noninvasive approaches to evaluate tendon microcirculation lack sensitivity and spatial coverage. PURPOSE: To develop a novel Achilles tendon intravoxel incoherent motion (IVIM) MRI protocol to overcome the limitations from low tendon T2 /T2 * value and low intratendinous blood volume and blood velocity to evaluate tendon microcirculation. STUDY TYPE: Prospective. SUBJECTS: Sixteen healthy male participants (age 31.0 ± 2.1) were recruited. FIELD STRENGTH/SEQUENCE: A stimulated echo readout-segmented echo planar imaging (ste-RS-EPI) IVIM sequence at 3.0T. ASSESSMENT: The feasibility of the proposed ste-RS-EPI IVIM protocol combined with Achilles tendon magic angle effect was evaluated. The sensitivity of the protocol was assessed by an exercise-induced intratendinous hemodynamic response in healthy participants. The vascular origin of the observed IVIM signal was validated by varying the diffusion mixing time and echo time. STATISTICAL TESTS: Two-tailed t-tests were used to evaluate differences (P < 0.05 was considered significant). RESULTS: Consistent with known tendon hypovascularity, the midportion Achilles tendon at baseline showed significantly lower IVIM-derived perfusion fraction (fp ) (3.1 ± 0.9%) compared to the proximal and distal Achilles tendon (6.0 ± 1.8% and 6.1 ± 2.0%, respectively; P < 0.01). Similarly, the midportion Achilles tendon exhibited significantly lower baseline blood flow index (D*×fp ) (40.9 ± 19.2, 18.3 ± 5.3, and 32.0 ± 9.4 in proximal, midportion, and distal Achilles tendon, respectively; P < 0.01). Eccentric heel-raise exercise led to ∼2 times increase of Achilles tendon blood flow in healthy participants. Consistent with its vascular origin, the estimated fp demonstrated a high dependency to IVIM protocol parameters, while the T1 /T2 -corrected absolute intratendinous microvascular blood volume fraction (Vb ) did not vary. DATA CONCLUSION: Achilles tendon ste-RS-EPI IVIM noninvasively assessed baseline values and exercise-induced changes to tendon microcirculation in healthy tendon. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1690-1699.

Is the T1ρ MRI profile of hyaline cartilage in the normal hip uniform?

BACKGROUND: T1ρ MRI is an imaging technique sensitive to proteoglycan (PG) content of hyaline cartilage. However, normative T1ρ values have not been established for the weightbearing cartilage of the hip, and it is not known whether it is uniform or whether there is topographic variation. Knowledge of the T1ρ profile of hyaline cartilage in the normal hip is important for establishing a baseline against which comparisons can be made to experimental and clinical arthritic subjects. QUESTIONS/PURPOSES: In this diagnostic study, we determined (1) the T1ρ MRI values of hyaline cartilage of the normal hip; and (2) whether the T1ρ MRI profile of the normal hip hyaline cartilage is uniform. METHODS: Fourteen asymptomatic volunteers (11 men, three women; mean age, 35 years) prospectively underwent 1.5-T T1ρ MRI of a single hip. The weightbearing hyaline cartilage bilayer of the acetabulum and femoral head was evaluated on sagittal images and segmented into four zones: (1) anterior; (2) anterosuperior; (3) posterosuperior; and (4) and posterior. For the full region of interest and within each zone and each sagittal slice, we calculated the mean T1ρ relaxation value, a parameter that indirectly quantifies PG content, where T1ρ is inversely related to PG concentration. RESULTS: There was variation in the T1ρ relaxation values depending on zone (anterior to posterior) and slice (medial to lateral). When combining the most anterior quadrants (Zones 1 and 2), the T1ρ relaxation values were lower than those in the combined posterior quadrants (Zones 3 and 4) (30.4 msec versus 32.2 msec, respectively; p = 0.002), reflecting higher PG concentration. There was a difference between the T1ρ relaxation values of the sagittal slices (p = 0.038), most pronounced anteriorly in Zone 1 (26.6 msec, p = 0.001). With a selective combination of zones and slices, there were lower mean T1ρ values in the anterolateral-most region compared with the remainder of the weightbearing portion of the hip (28.6 msec versus 32.2 msec, respectively; p = 0.001). CONCLUSIONS: The T1ρ profile of normal hyaline cartilage of the hip is not uniform with the topographic differences identified suggesting regional variations in PG concentration. This study, through determination of lower T1ρ relaxation values, suggests inherently greater PG concentrations in the more anterolateral region of the normal hip hyaline cartilage. Furthermore, it demonstrates that T1ρ MRI has the ability to detect even subtle, microscopic local differences in hyaline cartilage composition. This technique has the potential to facilitate basic science and clinical research by serving as a noninvasive surrogate or biomarker of cartilage health and thus may be added to the growing repertoire of advanced, biochemical MRI techniques for evaluating hyaline cartilage.

Breast cancer and bone metastases: the association of axial skeleton MRI findings with skeletal-related events and survival.

The purpose of this study was to determine if bone metastasis characteristics on axial skeleton MRI are associated with either skeletal-related events (SREs) or survival in breast cancer patients. A retrospective review was performed on 247 breast cancer patients with bone metastases identified on axial skeleton MRI. MRI studies were reviewed for metastases T1 signal, signal uniformity, complete vertebral metastatic marrow replacement, metastases quantity, and distribution. Odds ratio (OR) and hazard ratios (HR) were calculated, with 95 % confidence intervals (95 % CI), to determine association with either future SREs or survival. At the time of analysis, 174 (70 %) patients had developed SREs and 176 (71 %) patients were dead. Features of skeletal metastases associated with SREs included the presence of complete metastatic marrow replacement within any vertebra; OR 2.363 (95 % CI 1.240-4.504, P = 0.0090), and more widely distributed metastases; OR 1.239 (95 % CI 1.070-1.435, P = 0.0040). Features associated with shorter survival included the presence of complete metastatic marrow replacement within any vertebra; HR 1.500 (95 % CI 1.105-2.036, P = 0.0093), and more widely distributed metastases; HR 1.141 (95 % CI 1.047-1.243, P = 0.0027). Metastases T1 signal, signal uniformity, and surprisingly quantity were not associated with SREs or survival. Axial skeleton MRI was able to identify characteristics predictive of future SREs and survival. These characteristics could be used for risk stratification for future trials if prospectively validated.

The role of radiology in the evolution of the understanding of articular disease.

Both the clinical practice of radiology and the journal Radiology have had an enormous effect on our understanding of articular disease. Early descriptions of osteoarthritis (OA) appeared in Radiology. More recently, advanced physiologic magnetic resonance (MR) techniques have furthered our understanding of the early prestructural changes in patients with OA. Sodium imaging, delayed gadolinium-enhanced MR imaging of cartilage, and spin-lattice relaxation in the rotating frame (or T1ρ) sequences have advanced understanding of the pathophysiology and pathoanatomy of OA. Many pioneering articles on rheumatoid arthritis (RA) also have been published in Radiology. In the intervening decades, our understanding of the natural history of RA has been altered by these articles. Many of the first descriptions of crystalline arthropathies, including gout, calcium pyrophosphate deposition, and hydroxyapatite deposition disease, appeared in Radiology.

Tibial stress changes in new combat recruits for special forces: patterns and timing at MR imaging.

PURPOSE: To characterize the incidence, location, grade, and patterns of magnetic resonance (MR) imaging findings in the tibia in asymptomatic recruits before and after 4-month basic training and to investigate whether MR imaging parameters correlated with pretraining activity levels or with future symptomatic injury. MATERIALS AND METHODS: This study was approved by three institutional review boards and was conducted in compliance with HIPAA requirements. Volunteers were included in the study after they signed informed consent forms. MR imaging of the tibia of 55 men entering the Israeli Special Forces was performed on recruitment day and after basic training. Ten recruits who did not perform vigorous self-training prior to and during service served as control subjects. MR imaging studies in all recruits were evaluated for presence, type, length, and location of bone stress changes in the tibia. Anthropometric measurements and activity history data were collected. Relationships between bone stress changes, physical activity, and clinical findings and between lesion size and progression were analyzed. RESULTS: Bone stress changes were seen in 35 of 55 recruits (in 26 recruits at time 0 and in nine recruits after basic training). Most bone stress changes consisted of endosteal marrow edema. Approximately 50% of bone stress changes occurred between the middle and distal thirds of the tibia. Lesion size at time 0 had significant correlation with progression. All endosteal findings smaller than 100 mm resolved or did not change, while most findings larger than 100 mm progressed. Of 10 control subjects, one had bone stress changes at time 0, and one had bone stress changes at 4 months. CONCLUSION: Most tibial bone stress changes occurred before basic training, were usually endosteal, occurred between the middle and distal thirds of the tibia, were smaller than 100 mm, and did not progress. These findings are presumed to represent normal bone remodeling.