Christine B. Chung

Isl1Cre reveals a common Bmp pathway in heart and limb development

A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo.

Qualitative and quantitative ultrashort echo time (UTE) imaging of cortical bone.

We describe the use of two-dimensional ultrashort echo time (2D UTE) sequences with minimum TEs of 8 μs to image and quantify cortical bone on a clinical 3T scanner. An adiabatic inversion pulse was used for long T(2) water and fat signal suppression. Adiabatic inversion prepared UTE acquisitions with varying TEs were used for T(2) measurement. Saturation recovery UTE acquisitions were used for T(1) measurement. Bone water concentration was measured with the aid of an external reference phantom. UTE techniques were evaluated on cadaveric specimens and healthy volunteers. A signal-to-noise ratio of around 30, contrast-to-noise ratio of around 27/20 between bone and muscle/fat were achieved in tibia in vivo with a nominal voxel size of 0.23 × 0.23 × 6.0 mm(3) in a scan time of 5 min. A mean T(1) of 223 ± 11 ms and mean T(2) of 390 ± 19 μs were found. Mean bone water concentrations of 23.3 ± 1.6% with UTE and 21.7 ± 1.3% with adiabatic inversion prepared UTE sequences were found in tibia in five normal volunteers. The results show that in vivo qualitative and quantitative evaluation of cortical bone is feasible with 2D UTE sequences.

Fresh Osteochondral Allografts

Twenty knees in 18 patients were treated (mean age, 42 years; range, 19-64 years) with fresh osteochondral allografting limited to the patellofemoral joint. The knees were analyzed retrospectively to determine the rate of successful outcomes. The trochlea and patella were treated in 12 patients and the patella was treated in eight patients. There were 11 women and seven men. The primary outcome measures were revision allografting, arthrodesis, or arthroplasty, and clinical scoring using a modified Merle D’Aubigné-Postel 18-point scale. Radiographs were available for 12 knees. There were five failures. For the remaining knees, the clinical scores increased from a mean of 11.7 points (range, 7-15 points) to 16.3 points (range, 12-18 points). Of the knees evaluated radiographically, four had no evidence of patellofemoral arthrosis, and six had only mild arthrosis. Fresh osteochondral allografting is a salvage procedure for the young, active patient with severe articular cartilage disease of the patellofemoral joint. The results of this procedure are comparable to results of described other techniques in the literature. If allograft incorporation does occur, the procedure is associated with improved pain, function, range of motion, and a low risk of progressive arthritis. Level of Evidence: Level IV (case series-no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Complications of anterior cruciate ligament reconstruction: MR imaging.

Abstract. Arthroscopic reconstruction of the anterior cruciate ligament (ACL) using autografts or allografts is being performed with increasing frequency, particularly in young athletes. Although the procedure is generally well tolerated, with good success rates, early and late complications have been documented. As clinical manifestations of graft complications are often non-specific and plain radiographs cannot directly visualize the graft and the adjacent soft tissues, MR imaging has a definite role in the diagnosis of complications after ACL reconstruction and may direct subsequent therapeutic management. Our purpose is to review the normal MR imaging of the ACL graft and present the MR imaging findings of a wide spectrum of complications after ACL reconstruction, such as graft impingement, graft rupture, cystic degeneration of the graft, postoperative infection of the knee, diffuse and localized (i.e., cyclops lesion) arthrofibrosis, and associated donor site abnormalities. Awareness of the MR imaging findings of complications as well as the normal appearances of the normal ACL graft is essential for correct interpretation.

Quantitative ultrashort echo time (UTE) MRI of human cortical bone: Correlation with porosity and biomechanical properties

In this study we describe the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) to evaluate short and long T2* components as well as the water content of cortical bone. Fourteen human cadaveric distal femur and proximal tibia were sectioned to produce 44 rectangular slabs of cortical bone for quantitative UTE MR imaging, microcomputed tomography (µCT), and biomechanical testing. A two‐dimensional (2D) UTE pulse sequence with a minimal nominal TE of 8 µseconds was used together with bicomponent analysis to quantify the bound and free water in cortical bone using a clinical 3T scanner. Total water concentration was measured using a 3D UTE sequence together with a reference water phantom. UTE MR measures of water content (total, free, and bound), T2* (short and long), and short and long T2* fractions were compared with porosity assessed with µCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation. Porosity significantly correlated positively with total (R2 = 0.23; p < 0.01) and free (R2 = 0.31; p < 0.001) water content as well as long T2* fraction (R2 = 0.25; p < 0.001), and negatively with short T2* fraction and short T2* (R2 = 0.24; p < 0.01). Failure strain significantly correlated positively with short T2* (R2 = 0.29; p < 0.001), ultimate stress significantly correlated negatively with total (R2 = 0.25; p < 0.001) and bound (R2 = 0.22; p < 0.01) water content, and failure energy significantly correlated positively with both short (R2 = 0 30; p < 0.001) and long (R2 = 0.17; p < 0.01) T2* values. These results suggest that UTE MR measures are sensitive to the structure and failure properties of human cortical bone, and may provide a novel way of evaluating cortical bone quality.

Calcification in calcium pyrophosphate dihydrate (CPPD) crystalline deposits in the knee: anatomic, radiographic, MR imaging, and histologic study in cadavers.

ObjectiveTo demonstrate and determine the frequency and location of calcification within cadaveric knees with or without calcification typical of calcium pyrophosphate dihydrate (CPPD), utilizing histologic, radiographic and MR imaging techniques.Design and patientsTen cadaveric knees of elderly individuals that demonstrated no radiographic evidence of prior surgery or trauma were studied with MR imaging and subsequently sectioned in planes corresponding to those obtained with MR imaging. The slices were imaged with high-resolution radiography. Two musculoskeletal radiologists correlated the anatomic, MR and radiographic findings. Three of the knees, which did not demonstrate calcifications, were utilized as controls. Histologic sections were obtained from four knees that contained calcifications and from the three controls, and analyzed with special histologic stains that demonstrate phosphorus and calcium.ResultsRadiographic imaging and histologic analysis demonstrated widespread CPPD crystal deposition in four of the 10 knee specimens (40%). MR imaging demonstrated some calcifications only within the articular cartilage of the femoral condyles in three of the four (75%) specimens that had CPPD deposits. In all four specimens radiographs and histologic analysis were more sensitive than MR imaging. Histologic analysis demonstrated no evidence of CPPD crystals in the control specimens.ConclusionMR imaging is insensitive to the presence of CPPD deposits in the knee, even when such deposits are widespread. Our study suggests that the sensitivity of MR imaging was significantly better in detecting CPPD deposits in the hyaline cartilage of the femoral condyles when compared with other internal structures, even when such structures contained a higher amount of calcification.

Patellar tendon–lateral femoral condyle friction syndrome: MR imaging in 42 patients

Objective: To demonstrate the MR imaging findings that occur between the posterior inferolateral patellar tendon and the lateral femoral condyle in patients with chronic anterior and or lateral knee pain. Patients and design: A retrospective review of the MR images in 42 patients who presented with chronic anterior or lateral knee pain was performed by two musculoskeletal radiologists. In 15 patients, post-contrast images were available. Results: Sagittal and axial imaging planes best demonstrated the patellar tendon and its relationship with the lateral femoral condyle. In 40 patients, there was obliteration of the fat planes and abnormal signal intensity in the lateral soft tissues of the inferior patellofemoral joint. Enhancement after administration of gadolinium was noted in all cases in which contrast was administered. Eighteen patients showed cystic changes in the soft tissues adjacent to the lateral femoral condyle in addition to fat plane obliteration. In two patients, only cystic changes were noted in the lateral soft tissues. Abnormal patellar alignment was noted in 37 patients. Patellar tendon pathology was seen in nine patients. Conclusion: In evaluating anterior knee symptoms, MR imaging allows identification of changes that may be related to patellar tendon–lateral femoral condyle friction syndrome and that should be distinguished from other causes of anterior or lateral knee pain.

End plate marrow changes in the asymptomatic lumbosacral spine: frequency, distribution and correlation with age and degenerative changes.

PurposeTo investigate the frequency and distribution of end plate marrow signal intensity changes in an asymptomatic population and to correlate these findings with patient age and degenerative findings in the spine.Materials and methodsMR imaging studies of the lumbosacral (LS) spine in 59 asymptomatic subjects were retrospectively reviewed by 2 musculoskeletal radiologists to determine the presence and location of fat-like and edema-like marrow signal changes about the end plates of the L1-2 through L5-S1 levels. The presence of degenerative changes in the spine was recorded as was patient age. Descriptive statistics were utilized to determine the frequency and associations of end plate findings and degenerative changes in the spine. Interobserver variability was determined by a kappa score. Binomial probability was used to predict the prevalence of the end plate changes in a similar subject population. The Fisher exact test was performed to determine statistical significance of the relationship of end plate changes with degenerative changes in the spine, superior versus inferior location about the disc and age of the patient population.ResultsFocal fat-like signal intensity adjacent to the vertebral end-plate was noted in 15 out of 59 subjects by both readers, and involved 38 and 36 out of 590 end plates by readers 1 and 2, respectively. Focal edema-like signal intensity adjacent to the vertebral end plate was noted in 8 out of 59 subjects by both readers and involved 11 and 10 out of 590 end plates by readers 1 and 2, respectively. Either fat or edema signal intensity occurred most often at the anterior (p<.05) aspects of the mid-lumbar spine and was seen in an older sub-population of the study (p<.05).ConclusionEnd plate marrow signal intensity changes are present in the lumbar spine of some asymptomatic subjects with a characteristic location along the spine and in vertebral end plates.

Ultrashort echo time spectroscopic imaging (UTESI) of cortical bone

Cortical bone in the mature skeleton has a short T2* and produces no detectable signal with conventional MR sequences. A two‐dimensional ultrashort echo time (UTE) sequence employing half radio frequency (RF) pulse excitations and radial ramp sampling reduces the effective TE to 8 μs and is capable of detecting signals from cortical bone. We propose a time‐efficient UTE spectroscopic imaging (UTESI) technique based on an interleaved variable TE acquisition, preceded by long T2* signal suppression using either a 90° pulse and gradient dephasing or an inversion pulse and nulling. The projections were divided into multiple groups with the data for each group being collected with progressively increasing TE and interleaved projection angles. The undersampled projections within each group sparsely covered k‐space. A view sharing and sliding window reconstruction algorithm was implemented to reconstruct images at each TE, followed by Fourier transformation in the time domain to generate spectroscopic images. T2* was quantified through either exponential fitting of the time domain images or line fitting of the magnitude spectrum. Relative water content and the resonance frequency shift due to bulk susceptibility were also evaluated. The feasibility of this technique was demonstrated with phantom and volunteer studies on a clinical 3T scanner. Magn Reson Med 58:1001–1009, 2007.

Short T2 contrast with three-dimensional ultrashort echo time imaging.

There is increasing interest in imaging short T2 species which show little or no signal with conventional magnetic resonance (MR) pulse sequences. In this paper, we describe the use of three-dimensional ultrashort echo time (3D UTE) sequences with TEs down to 8 μs for imaging of these species. Image contrast was generated with acquisitions using dual echo 3D UTE with echo subtraction, dual echo 3D UTE with rescaled subtraction, long T2 saturation 3D UTE, long T2 saturation dual echo 3D UTE with echo subtraction, single adiabatic inversion recovery 3D UTE, single adiabatic inversion recovery dual echo 3D UTE with echo subtraction and dual adiabatic inversion recovery 3D UTE. The feasibility of using these approaches was demonstrated in in vitro and in vivo imaging of calcified cartilage, aponeuroses, menisci, tendons, ligaments and cortical bone with a 3-T clinical MR scanner. Signal-to-noise ratios and contrast-to-noise ratios were used to compare the techniques.