The visible skeleton 2.0: phenotyping of cartilage and bone in fixed vertebrate embryos and foetuses based on X-ray microCT.

For decades, clearing and staining with Alcian Blue and Alizarin Red has been the gold standard to image vertebrate skeletal development. Here, we present an alternate approach to visualise bone and cartilage based on X-ray microCT imaging, which allows the collection of genuine 3D data of the entire developing skeleton at micron resolution. Our novel protocol is based on ethanol fixation and staining with Ruthenium Red, and efficiently contrasts cartilage matrix, as demonstrated in whole E16.5 mouse foetuses and limbs of E14 chicken embryos. Bone mineral is well preserved during staining, thus the entire embryonic skeleton can be imaged at high contrast. Differences in X-ray attenuation of ruthenium and calcium enable the spectral separation of cartilage matrix and bone by dual energy microCT (microDECT). Clearing of specimens is not required. The protocol is simple and reproducible. We demonstrate that cartilage contrast in E16.5 mouse foetuses is adequate for fast visual phenotyping. Morphometric skeletal parameters are easily extracted. We consider the presented workflow to be a powerful and versatile extension to the toolkit currently available for qualitative and quantitative phenotyping of vertebrate skeletal development.

Preoperative Imaging of Costal Cartilage to Aid Reconstructive Head and Neck Surgery: A Systematic Review.

OBJECTIVE: Autologous costal cartilage is used extensively in reconstructive surgery because of its stability, durability, and biocompatibility. The current preoperative evaluation of costal cartilage often only consists of a physical examination. Several studies have highlighted the benefits of preoperative imaging as a tool to ensure optimal graft harvest. This systematic review aims to synthesize the current evidence and establish the efficacy of the various imaging modalities for the assessment of costal cartilage. REVIEW METHODS: The data sources were explored using a search strategy based on the terms ("costal cartilage" OR "ribs" AND "imaging*") combined with Boolean operators. The primary outcome measures were the ability to measure the dimensions of costal cartilages and to detect the presence of calcifications. RESULTS: A total of 28 publications were included in the final review, with 12 case series, 7 case control studies, and 9 cohort studies. Twenty-two studies used computed tomography (CT); 4 studies used x-ray and 2 studies used ultrasonography, whereas no studies used magnetic resonance imaging. Meta-analysis of the data from these studies was not deemed possible. CONCLUSIONS: Our findings suggest that CT is the modality with the strongest evidence base that provides the greatest degree of information. The major benefits of CT are its ability to provide 3-dimensional image reconstruction for surgical planning, ability to detect synchondroses, and assess cartilage quality. Where radiation exposure is less preferable, x-ray and ultrasound (US) may play an important role. X-ray appears to be particularly useful when the main concern is the presence of calcification. The limited studies available indicate that US can provide useful and accurate information on cartilage quality and morphology. Further studies are warranted in exploring the use of US in preoperative planning, particularly in the pediatric population.

Cartilaginous endplate avulsion is associated with modic changes and endplate defects, and residual back and leg pain following lumbar discectomy.

OBJECTIVE: While cartilaginous endplate (CEP) avulsion is a common finding in discectomy due to lumbar disc herniation, its roles in residual back and leg pain, associations with Modic changes (MCs) and endplate defects (EPD) remain unknown. DESIGN: Patients with a single-level lumbar disc herniation who underwent endoscopic discectomy were studied. On MR images, the adjacent endplates of the herniated disc were assessed for MCs and EPD. The presence of CEP avulsion was examined under endoscopic and visualized inspection. Back and leg pain were evaluated by a numeric rating scale (NRS) and the Oswestry Disability Index. Associations of CEP avulsion with adjacent MCs, EPD, and residual back and leg pain were examined. In addition, histological features of avulsed CEP were determined using gross staining and immunohistochemical methods. RESULTS: A total of 386 patients were included. CEP avulsion was found in 166 (43%) patients, and adjacent MCs and EPD were observed in 117 (30.3%) and 139 (36%) patients. The presence of CEP avulsion was associated with greater age, adjacent MCs (OR = 2.60, 95%CI [1.61-4.19]) and EPD (OR = 1.63, 95%CI [1.03-2.57]). Among the 187 patients with ≥2 years follow-up, CEP avulsion was associated with residual back pain (OR = 2.49, 95%CI [1.29-4.82]) and leg pain (OR = 2.25, 95%CI [1.04-4.84]). Histologically, the avulsed CEP was characterized by multiple defects, apparent inflammation, and nucleus invasion, as well as the upregulation of IL-1ß, caspase-1, and NLRP3 inflammasome. CONCLUSION: CEP avulsion was associated with MCs, EPD, and residual back and leg pain after discectomy, which may be attributed to NLRP3 inflammasome related inflammations.

Serum uric acid and knee osteoarthritis in community residents without gout: a longitudinal study.

OBJECTIVES: Emerging evidence suggests a potential link between OA and gout; however, the association between serum uric acid (UA) itself and knee OA remains uncertain due to a lack of longitudinal studies. Here, we investigated the association between serum UA and knee OA according to cartilage status in elderly community residents without gout. METHODS: In this longitudinal study, participants without a history of gout were recruited from among the Korean cohort of the Hallym Aging Study (n = 296 for radiography study and n = 223 for MRI study). Weight-bearing knee radiographs and 1.5-T MRI scans, along with blood collection for analysis of serum UA, were performed at baseline and after 3 years. The severity and structural progression of knee OA were evaluated using the Kellgren-Lawrence grading system and the Whole-Organ MRI Score (WORMS) cartilage scoring method. Multivariable logistic regression analysis was conducted using generalized estimating equation (GEE) models. RESULTS: Serum UA levels were not associated with radiographic progression after adjusting for age, sex and BMI. There was no significant association between serum UA and tibiofemoral cartilage loss on MRI. However, baseline serum UA levels were negatively associated with patellofemoral cartilage loss over 3 years (adjusted odd ratio 0.70 per 1 mg/dl increase, 95% CI: 0.49, 0.98). CONCLUSION: In this population-based cohort, serum UA was not a risk factor for knee OA progression. Further large-scale longitudinal studies in other populations are needed to validate the effects of UA on cartilage damage.

High-contrast osteochondral junction imaging using a 3D dual adiabatic inversion recovery-prepared ultrashort echo time cones sequence.

While conventional MRI sequences cannot visualize tissues from the osteochondral junction (OCJ) due to these tissues' short transverse T2 /T2 * relaxations, ultrashort echo time (UTE) sequences can overcome this limitation. A 2D UTE sequence with a dual adiabatic inversion recovery preparation (DIR-UTE) for selective imaging of short T2 tissues with high contrast has previously been developed, but high sensitivity to eddy currents and aliased out-of-slice excitation make it difficult to image the thin layer of the OCJ in vivo. Here, we combine the DIR scheme with a 3D UTE cones sequence for volumetric imaging of OCJ tissues in vivo, aiming to generate higher OCJ contrast compared with a recently developed single IR-prepared UTE sequence with a fat saturation module (IR-FS-UTE). All sequences were implemented on a 3-T clinical scanner. The DIR-UTE cones sequence combined a 3D UTE cones sequence with two narrow-band adiabatic IR preparation pulses centered on water and fat spectrum frequencies, respectively. The 3D DIR-UTE cones sequence was first applied to a phantom, then to the knees of four healthy volunteers and four patients diagnosed with osteoarthritis and compared with the IR-FS-UTE sequence. In both phantom and volunteer studies, the proposed DIR-UTE cones sequence showed much higher contrast for OCJ imaging than the IR-FS-UTE sequence did. The 3D DIR-UTE cones sequence showed a significantly higher contrast-to-noise ratio between the OCJ and subchondral bone fat (mean, standard deviation [SD]: 25.7 ± 2.3) and between the OCJ and superficial layers of cartilage (mean, SD: 22.2 ± 3.5) compared with the IR-FS-UTE sequence (mean, SD: 10.8 ± 2.5 and 16.3 ± 2.6, respectively). The 3D DIR-UTE cones sequence is feasible for imaging of the OCJ region of the knee in vivo and produces both high resolution and high contrast.

High contrast cartilaginous endplate imaging using a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence.

Ultrashort echo time (UTE) sequences can image tissues with transverse T 2 /T 2 * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast.

T2 mapping of the acetabular cartilage in infants and children with developmental dysplasia of the hip.

BACKGROUND: T2 mapping is useful for evaluating the cartilage matrix. PURPOSE: To determine the variations in the acetabular cartilage T2 relaxation values between healthy individuals and those with developmental dysplasia of the hip (DDH). MATERIAL AND METHODS: Thirty-three patients with unilateral DDH underwent 3-T magnetic resonance imaging (MRI) between January 2018 and February 2019. Fifteen volunteers (30 hips) were enrolled as controls. T2 values were measured with the T2 mapping sequence in all layers and were equally divided into three layers (deep, middle, and superficial) with equal thickness. We calculated the mean T2 relaxation values for the full thickness, deep, middle, and superficial layers and compared the values between the different groups. In addition, the inter- and intra-observer agreements were calculated. RESULTS: The T2 relaxation values in the DDH arm were significantly lower in the middle, superficial, and full thickness layers compared with those of the volunteers and contralateral hips. The T2 relaxation values of the deep layers showed no significant difference between the different groups. The acetabular cartilage T2 relaxation values increased from the deep layer to the superficial layer in the control and contralateral groups. Both inter- and intra-observer agreements were good. CONCLUSION: MRI T2 mapping may help to diagnose developmental disorders of the acetabular cartilage matrix in infants and children with DDH. Abnormal acetabular cartilage T2 relaxation values may be due to the extraordinary stress load of the femoral head.

Midterm Follow-Up and Assessment of Cartilage Thickness by Arthro-Magnetic Resonance Imaging After Arthroscopic Cam Resection, Labral Repair, and Rim Trimming Without Labral Detachment.

PURPOSE: To evaluate the clinical and radiological outcome, sum of acetabular and femoral cartilage thickness, and rate of failure in the midterm after arthroscopic treatment of femoroacetabular impingement (FAI) syndrome with femoral osteoplasty, labral repair, and rim trimming without labral detachment. METHODS: This retrospective case series included patients with FAI syndrome who had undergone hip arthroscopy from January 2009 to December 2010 by a single surgeon, with a minimum follow-up of 55 months. Data from patients who had undergone arthroscopic hip procedures with labral repair, rim trimming, and femoral osteoplasty were analyzed pre- and postoperatively. Clinical outcome (nonarthritic hip score [NAHS], Short Form 36 [SF-36]), range of motion, progression of osteoarthritis (Tönnis grade), radiological parameters (α angle, lateral center-edge angle [LCEA], Tönnis angle), femoral and acetabular cartilage thickness (using magnetic resonance imaging [MRI]), and intraoperative findings were evaluated. RESULTS: Of 148 hip arthroscopies performed, 97 included rim trimming, labral refixation, and femoral osteoplasty. Ten cases were lost to follow-up, leaving 87 hips. Arthroscopic revision was performed on 4 hips and total hip replacement on 4 hips, and 1 hip underwent both arthroscopic revision and total hip replacement. Excluding these 9 cases of revision, for which follow-up was not possible (retrospective study), the remaining 78 hips were followed up for a minimum of 55 months (77 ± 11.4, mean ± SD; range 55 to 124). Mean NAHS (65 to 88, P < .001), SF-36 physical subscale (65 to 85, P < .001), and the numerical pain rating scale (NRS) (5 to 1, P < .001) improved significantly. Outcome scores of minimal clinical importance (NAHS) were achieved in 67.6% of the patients. Mean range of movement improved significantly in flexion (109 to 122, P < .001) and internal rotation (10 to 22.7, P < .001). NAHS was positively associated with flexion of the hip postoperatively (r = 0.307, P = .011). In 16 cases, microfracture was performed (15 acetabular and 1 femoral). Preoperative α angles (anteroposterior and modified Dunn) were significantly higher in this cohort (P < .001, 95% confidence interval 8.9 to 25.2, P = .001). Twenty hips (28 %) progressed to worse Tönnis grades. Initial Tönnis grades were grade 0, 38; grade 1, 48; grade 2, 8. Pre- or postoperative Tönnis grades did not show any correlation with pre- or postoperative NAHS and NRS. MRI measurements at the latest follow-up (69 patients) of the femoral and acetabular cartilage thickness did not reveal any significant reduction at the 12 o'clock position. CONCLUSION: Arthroscopic cam resection, rim trimming, and labral repair without detachment of the labrum provides good or excellent outcome in 77.1% of hips based on NAHS in the midterm. Higher range of motion in flexion is associated with higher NAHS postoperatively. Arthroscopic cam resection, rim trimming and labral repair without detachment of the labrum is a successful method for the treatment of FAI syndrome in the midterm. LEVEL OF EVIDENCE: IV, retrospective case series.

Phosphotungstic acid-enhanced microCT: Optimized protocols for embryonic and early postnatal mice.

BACKGROUND: Given the need for descriptive and increasingly mechanistic morphological analyses, contrast-enhanced microcomputed tomography (microCT) represents perhaps the best method for visualizing 3D biological soft tissues in situ. Although staining protocols using phosphotungstic acid (PTA) have been published with beautiful visualizations of soft tissue structures, these protocols are often aimed at highly specific research questions and are applicable to a limited set of model organisms, specimen ages, or tissue types. We provide detailed protocols for micro-level visualization of soft tissue structures in mice at several embryonic and early postnatal ages using PTA-enhanced microCT. RESULTS: Our protocols produce microCT scans that enable visualization and quantitative analyses of whole organisms, individual tissues, and organ systems while preserving 3D morphology and relationships with surrounding structures, with minimal soft tissue shrinkage. Of particular note, both internal and external features of the murine heart, lungs, and liver, as well as embryonic cartilage, are captured at high resolution. CONCLUSION: These protocols have broad applicability to mouse models for a variety of diseases and conditions. Minor experimentation in the staining duration can expand this protocol to additional age groups, permitting ontogenetic studies of internal organs and soft tissue structures within their 3D in situ position.

Fully automated patellofemoral MRI segmentation using holistically nested networks: Implications for evaluating patellofemoral osteoarthritis, pain, injury, pathology, and adolescent development.

PURPOSE: Our clinical understanding of the relationship between 3D bone morphology and knee osteoarthritis, as well as our ability to investigate potential causative factors of osteoarthritis, has been hampered by the time-intensive nature of manually segmenting bone from MR images. Thus, we aim to develop and validate a fully automated deep learning framework for segmenting the patella and distal femur cortex, in both adults and actively growing adolescents. METHODS: Data from 93 subjects, obtained from on institutional review board-approved protocol, formed the study database. 3D sagittal gradient recalled echo and gradient recalled echo with fat saturation images and manual models of the outer cortex were available for 86 femurs and 90 patellae. A deep-learning-based 2D holistically nested network (HNN) architecture was developed to automatically segment the patella and distal femur using both single (sagittal, uniplanar) and 3 cardinal plane (triplanar) methodologies. Errors in the surface-to-surface distances and the Dice coefficient were the primary measures used to quantitatively evaluate segmentation accuracy using a 9-fold cross-validation. RESULTS: Average absolute errors for segmenting both the patella and femur were 0.33 mm. The Dice coefficients were 97% and 94% for the femur and patella. The uniplanar, relative to the triplanar, methodology produced slightly superior segmentation. Neither the presence of active growth plates nor pathology influenced segmentation accuracy. CONCLUSION: The proposed HNN with multi-feature architecture provides a fully automatic technique capable of delineating the often indistinct interfaces between the bone and other joint structures with an accuracy better than nearly all other techniques presented previously, even when active growth plates are present.

Skeletal deterioration in COL2A1-related spondyloepiphyseal dysplasia occurs prior to osteoarthritis.

OBJECTIVE: Spondyloepiphyseal dysplasia, a combination of progressive arthropathy with variable signs of skeletal dysplasia, can be a result of mutations in the collagen, type II, alpha 1 (COL2A1) gene. However, the bone involvement (e.g., density, microstructure) in this disorder has hitherto not been studied. DESIGN: A 50-year-old female patient and her 8-year-old son with flattening of vertebral bodies and early-onset osteoarthritis were genetically tested using a custom designed gene bone panel including 386 genes. Bone microstructure and turnover were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum bone turnover markers, respectively. Furthermore, the bone and cartilage phenotype of male mice heterozygous for the loss-of-function mutation of Col2a1 (Col2a1+/d) was analyzed compared to wildtype littermates using µ-CT and histomorphometry. RESULTS: We identified a dominant COL2A1 mutation (c.620G > A p.(Gly207Glu)) indicating spondyloepiphyseal dysplasia in the female patient and her son, both being severely affected by skeletal deterioration. Although there was no osteoarthritis detectable at first visit, the son was affected by trabecular osteopenia, which progressed over time. In an iliac crest biopsy obtained from the mother, osteoclast indices were remarkably increased. Col2a1+/d mice developed a moderate skeletal phenotype expressed by reduced cortical and trabecular parameters at 4 weeks. Importantly, no articular defects could be observed in the knee joints at 4 weeks, while osteoarthritis was only detectable in 12-week-old mice. CONCLUSIONS: Our results indicate that collagen type II deficiency in spondyloepiphyseal dysplasia leads to skeletal deterioration with early-onset in humans and mice that occurs prior to the development of osteoarthritis.

Deep learning-based fully automatic segmentation of wrist cartilage in MR images.

The study objective was to investigate the performance of a dedicated convolutional neural network (CNN) optimized for wrist cartilage segmentation from 2D MR images. CNN utilized a planar architecture and patch-based (PB) training approach that ensured optimal performance in the presence of a limited amount of training data. The CNN was trained and validated in 20 multi-slice MRI datasets acquired with two different coils in 11 subjects (healthy volunteers and patients). The validation included a comparison with the alternative state-of-the-art CNN methods for the segmentation of joints from MR images and the ground-truth manual segmentation. When trained on the limited training data, the CNN outperformed significantly image-based and PB-U-Net networks. Our PB-CNN also demonstrated a good agreement with manual segmentation (Sørensen-Dice similarity coefficient [DSC] = 0.81) in the representative (central coronal) slices with a large amount of cartilage tissue. Reduced performance of the network for slices with a very limited amount of cartilage tissue suggests the need for fully 3D convolutional networks to provide uniform performance across the joint. The study also assessed inter- and intra-observer variability of the manual wrist cartilage segmentation (DSC = 0.78-0.88 and 0.9, respectively). The proposed deep learning-based segmentation of the wrist cartilage from MRI could facilitate research of novel imaging markers of wrist osteoarthritis to characterize its progression and response to therapy.

Imaging Biomarkers of the Physis: Cartilage Volume on MRI vs. Tract Volume and Length on Diffusion Tensor Imaging.

BACKGROUND: Current methods to predict height and growth failure are imprecise. MRI measures of physeal cartilage are promising biomarkers for growth. PURPOSE: In the physis, to assess how 3D MRI volume measurements, and diffusion tensor imaging (DTI) measurements (tract volume and length) correlate with growth parameters and detect differences in growth. We compared patients exposed to cis-retinoic acid, which causes physeal damage and growth failure, with normal subjects. STUDY TYPE: Case-control. POPULATION: Twenty pediatric neuroblastoma survivors treated with cis-retinoic acid and 20 age- and sex-matched controls. FIELD STRENGTH/SEQUENCE: 3T; DTI and 3D double-echo steady-state (DESS) sequences. ASSESSMENT: On distal femoral MR studies, physeal 3D volume and DTI tract measurements were calculated and compared to height. STATISTICAL TESTS: We used partial Spearman correlation, analysis of covariance, logistic regression, Wald test, and the intraclass correlation coefficient (ICC). RESULTS: The height percentile correlated most strongly with DTI tract volumes (r = 0.74), followed by mean tract length (r = 0.53) and 3D volume (r = 0.40) (all P < 0.02). Only tract volumes and lengths correlated with annualized growth velocity. Relative to controls, patients showed smaller tract volumes (8.00 cc vs. 13.71 cc, P < 0.01), shorter tract lengths (5.92 mm vs 6.99 mm, P = 0.03), and smaller ratios of 3D cartilage volume to tract length; but no difference (4.51 cc vs 4.85 cc) in 3D MRI volumes. The 10 patients with the lowest height percentiles had smaller tract volumes (5.07 cc vs. 10.93 cc, P < 0.01), but not significantly different 3D MRI volumes. Tract volume is associated with abnormal growth, with an accuracy of 75%. DATA CONCLUSION: DTI tract volume of the physis/metaphysis predicts abnormal growth better than physeal cartilage volumetric measurement and correlates best with height percentile and growth velocity. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2 J. Magn. Reson. Imaging 2020;52:544-551.

Comparison of diagnostic performance between CT and MRI for detection of cartilage invasion for primary tumor staging in patients with laryngo-hypopharyngeal cancer: a systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of contrast-enhanced CT with that of MRI in the detection of cartilage invasion in patients with laryngo-hypopharyngeal cancer. METHODS: A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting diagnostic accuracy of CT and/or MRI in detecting cartilage invasion from laryngo-hypopharyngeal cancer between 2000 and 2018. The pooled sensitivity and specificity, and their 95% confidence intervals were calculated for CT and MRI using bivariate random effects modeling. Subgroup and meta-regression analyses were performed. Indirect comparison was also performed by univariable meta-regression. RESULT: Fourteen articles including 776 patients were included in the systematic review and meta-analysis: eight for CT, and six for MRI. CT and MRI showed pooled sensitivities of 66% (95% CI, 49-80%) and 88% (95% CI, 79-93%), and pooled specificities of 90% (95% CI, 82-94%) and 81% (95% CI, 76-84%), respectively. MRI showed significantly higher sensitivity than CT (p = 0.02). The specificities showed no statistically significant difference between CT and MRI (p = 0.39). The CT studies showed heterogeneity and a threshold effect, while MRI showed neither heterogeneity nor threshold effect. In the meta-regression analysis for CT, the type of cartilage analyzed (thyroid only vs. thyroid/cricoid/arytenoid, p < 0.001) was a significant factor influencing the heterogeneity in the diagnostic performance of the CT studies. CONCLUSIONS: In conclusion, MRI has significantly higher sensitivity than CT for detecting cartilage invasion in patients with laryngo-hypopharyngeal cancer, without a significant difference in the specificity. KEY POINTS: • MRI has significantly higher sensitivity than CT for detecting cartilage invasion in patients with laryngo-hypopharyngeal cancer.

High Risk of Mismatch Between Sanders and Risser Staging in Adolescent Idiopathic Scoliosis: Are We Guiding Treatment Using the Wrong Classification?

BACKGROUND: Despite known limitations, Risser staging has traditionally been the primary marker of skeletal maturity utilized in decision-making for treatment of adolescent idiopathic scoliosis (AIS). The purpose of this study is to assess the incidence and factors associated with mismatch between Risser Staging and Sanders classification, and determine interobserver reliability. METHODS: We reviewed the medical records of consecutive patients aged 10 to 18 referred to our institution for evaluation of AIS from January to June 2016 with a closed triradiate cartilage. Data collected included sex, age, race, height, weight, body mass index percentile, menarchal status, Risser stage, Sanders classification, and major curve. Risser and Sanders stage was determined by 2 fellowship-trained pediatric spine surgeons and 1 pediatric orthopaedic nurse practitioner. Mismatch was defined as Risser stage 2 to 4 corresponding to Sanders 3 to 5, and Risser 0 to 1 corresponding to Sanders 6 to 7. RESULTS: A total of 165 consecutive patients were identified (mean age: 13.9±1.7 y, major curve 28.2±15.4 degrees, 76% female). The risk of skeletal maturity mismatch, based on the criteria of Risser 2 to 5 (limited growth remaining) corresponding to Sanders 3 to 5 (significant growth remaining) was 21.8%, indicating that 1 of 5 patients would be undertreated if managed by Risser criteria. Conversely, the mismatch risk for Risser 0 to 1 corresponding to Sanders 6 to 7 was 3.6%, leading such patients to be treated conservatively longer than necessary. Males and those of Hispanic ethnicity were at a higher risk of mismatch (23.1% vs. 11.9%, P=0.08; 33.3% vs. 8.8%, P=0.04, respectively). Body mass index percentile, race, and major curve were not associated with mismatch. The unweighted and weighted interobserver κ for Risser staging was 0.74 and 0.82, respectively, and 0.86 and 0.91 for Sanders classification, respectively. CONCLUSION: Given the limited sensitivity of Risser staging during peak growth velocity, high mismatch risk, and lower interobserver reliability, the Sanders classification should be utilized to guide treatment options in patients with AIS. Compared with Sanders, utilizing Risser staging results in mistreatment in a total of 1 of 4 patients, with the vast majority being undertreated. LEVEL OF EVIDENCE: Level II.

Heminasal Reconstruction Utilizing Presurgical Planning, Template-Based Cartilage Reconstruction and Tissue Expansion.

Heminasal aplasia is a rare congenital nasal anomaly in which there is unilateral deficiency in both the external nasal anatomy and nasal airway. Unilateral failure in development of a nasal placode in embryogenesis is thought to be the underlying cause of this anomaly. The authors describe the reconstruction of heminasal aplasia in a teenager utilizing a templated cartilaginous framework and tissue expansion. The authors feel the satisfactory results of this technique will be of benefit to other surgeons who may encounter this rare anomaly.

T2 relaxation time bias in gagCEST at 3T and 7T: comparison of saturation schemes.

PURPOSE: To characterize the effects of water T2 relaxation time in the glycosaminoglycan chemical exchange saturation transfer method (gagCEST) and compare them between 3T and 7T as well as between various saturation schemes. METHODS: Simulations and a phantom experiment were conducted at 3T and 7T in a range of water T2 values and GAG concentrations using various saturation schemes. For both simulations and MRI measurements, unsaturated signal as well as the saturated Z-spectrum were generated, and the magnetization transfer ratio asymmetry at 1 parts per million was used as a measure of the gagCEST effect size. RESULTS: The simulations and phantom experiment results showed a clear GAG concentration and T2 dependence of the gagCEST effect size. Whereas the gagCEST effect size was much larger at 7T, the impact of the T2 bias was more pronounced at 3T. The saturation train length, duty cycle, and average B1 all had clear impact on both the gagCEST effect size and T2 bias. CONCLUSION: The water T2 relaxation is important to consider in gagCEST, especially at 3T. The T2 differences can introduce a pronounced bias, which may obscure the gagCEST effect when using low duty cycles and long saturation trains.

SNR-weighted regularization of ADC estimates from double-echo in steady-state (DESS).

PURPOSE: To improve the homogeneity and consistency of apparent diffusion coefficient (ADC) estimates in cartilage from the double-echo in steady-state (DESS) sequence by applying SNR-weighted regularization during post-processing. METHODS: An estimation method that linearizes ADC estimates from DESS is used in conjunction with a smoothness constraint to suppress noise-induced variation in ADC estimates. Simulations, phantom scans, and in vivo scans are used to demonstrate how the method reduces ADC variability. Conventional diffusion-weighted echo-planar imaging (DW EPI) maps are acquired for comparison of mean and standard deviation (SD) of the ADC estimate. RESULTS: Simulations and phantom scans demonstrated that the SNR-weighted regularization can produce homogenous ADC maps at varying levels of SNR, whereas non-regularized maps only estimate ADC accurately at high SNR levels. The in vivo maps showed that the SNR-weighted regularization produced ADC maps with similar heterogeneity to maps produced with standard DW EPI, but without the distortion of such reference scans. CONCLUSION: A linear approximation of a simplified model of the relationship between DESS signals allows for fast SNR-weighted regularization of ADC maps that reduces estimation error in relatively short T2 tissue such as cartilage.

Stabilization of T2 relaxation and magnetization transfer in cartilage explants by immersion in perfluorocarbon liquid.

PURPOSE: Magnetic resonance imaging of ex vivo cartilage measures parameters such as T2 and magnetization transfer ratio (MTR), which reflect structural changes associated with osteoarthritis. Samples are often immersed in aqueous solutions to prevent dehydration and to to improve susceptibility matching. This study sought to determine the extent to which T2 and MTR changes are attributable to immersion alone and to identify immersion conditions to minimize this confounding factor. METHODS: T2 and MTR were measured before and after immersion for up to 24 hours at 4°C. Bovine nasal and articular cartilage and human articular cartilage were studied. Experimental groups included undisturbed immersion in Fluorinert FC-770, a susceptibility-matched, hydrophobic liquid with minimal tissue penetration, and immersion in Fluorinert, Dulbecco's phosphate-buffered saline (DPBS), or saline, with removal from the magnet between scans. 19 F and 1 H-MRI were used to detect cartilage penetration by Fluorinert and swelling, respectively. RESULTS: Saline and DPBS immersion rapidly increased T2 , wet weight and cartilage volume and decreased MTR, suggesting increased water content for all cartilage types. Fluorinert-immersed samples exhibited minimal changes in T2 or MTR. No ingress of Fluorinert was detected after 2 weeks of continuous immersion at 4°C. CONCLUSION: Ex vivo quantitative MR studies of cartilage may be confounded by the effects of immersion in aqueous solution, which may be comparable to or larger than effects attributed to pathology. These effects may be mitigated by immersion in perfluorocarbon liquids such as Fluorinert FC-770.

Whole knee joint T1 values measured in vivo at 3T by combined 3D ultrashort echo time cones actual flip angle and variable flip angle methods.

PURPOSE: To measure T1 relaxations for the major tissues in whole knee joints on a clinical 3T scanner. METHODS: The 3D UTE-Cones actual flip angle imaging (AFI) method was used to map the transmission radiofrequency field (B1 ) in both short and long T2 tissues, which was then used to correct the 3D UTE-Cones variable flip angle (VFA) fitting to generate accurate T1 maps. Numerical simulation was carried out to investigate the accuracy of T1 measurement for a range of T2 values, excitation pulse durations, and B1 errors. Then, the 3D UTE-Cones AFI-VFA method was applied to healthy volunteers (N = 16) to quantify the T1 of knee tissues including cartilage, meniscus, quadriceps tendon, patellar tendon, anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), marrow, and muscles at 3T. RESULTS: Numerical simulation showed that the 3D UTE-Cones AFI-VFA technique can provide accurate T1 measurements (error <1%) when the tissue T2 is longer than 1 ms and a 150 µs excitation RF pulse is used and therefore is suitable for most knee joint tissues. The proposed 3D UTE-Cones AFI-VFA method showed an average T1 of 1098 ± 67 ms for cartilage, 833 ± 47 ms for meniscus, 800 ± 66 ms for quadriceps tendon, 656 ± 43 ms for patellar tendon, 873 ± 38 ms for ACL, 832 ± 49 ms for PCL, 379 ± 18 ms for marrow, and 1393 ± 46 ms for muscles. CONCLUSION: The 3D UTE-Cones AFI-VFA method allows volumetric T1 measurement of the major tissues in whole knee joints on a clinical 3T scanner.