Comparison of hippocampal volume measurement by autopsy and post-mortem magnetic resonance imaging.

We present an autopsy-validated, non-invasive, magnetic resonance imaging (MRI) based segmentation algorithm, for determining hippocampal volume. A segmentation algorithm was developed to assess the volume of the hippocampus. Deceased individuals with severe mental illness were used to evaluate the use of MRI imaging to determine hippocampal volume as this group has previously been associated with altered hippocampal volume diagnosed on MRI. The accuracy of the MR- scanning protocol for volume measurement was tested on a water filled phantom control with a known volume of 500 ml, and a difference of 0.08% was found. Thus the scanning protocol was deemed to have produced acceptable results when comparing volume measures of a pair of segmented hippocampi obtained at the 1 T MR scanner and a 3 T MR scanner using the software program Mimics®. The segmentation algorithm was tested by a volume comparison obtained using anterior and posterior landmarks (in situ) and the exact volume of the dissected hippocampus (ex situ). The in situ and ex situ hippocampal volumes were highly correlated; R2 was 96%, with a mean difference of 4-5%. Cases were also examined for intra- and inter-observer agreement. This study presents a validated segmentation algorithm that can be used to determine the hippocampal volume using post-mortem MR and anatomical landmarks.

A Prospective Study Comparing 99mTc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with 18F-Fluoride PET/CT and 18F-Fluoride PET/MRI for Diagnosing Bone Metastases.

We prospectively evaluated and compared the diagnostic performance of 99mTc-hydroxyethylene-diphosphonate (99mTc-HDP) planar bone scintigraphy (pBS), 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and 18F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18F-NaF PET/CT within 9 d. 18F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion:18F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.

Osseous osteoarthritic-like changes and joint mobility of the temporomandibular joints and upper cervical spine: is there a relation?

OBJECTIVES: To compare 1) temporomandibular joint (TMJ) mobility between patients with and without reduced upper cervical spine (UCS) mobility and with and without TMJ osseous osteoarthritic-like changes, and 2) UCS osseous changes between patients with and without TMJ osseous osteoarthritic-like changes and with and without reduced UCS mobility. STUDY DESIGN: The study comprised 39 patients without pain from TMJ or UCS and with obstructive sleep apnea, 15 women (age range 26-72 years, mean 56.0) and 24 men (age range 27-71 years, mean 49.8). The range of motion (ROM) of the mandible and UCS was assessed clinically. Osseous changes of the TMJ and UCS were assessed by cone beam computed tomography. Differences were tested and adjusted for age and gender by multiple linear and logistic regression analyses. RESULTS: The mandibular ROM was within normal range (45-64 mm) but the UCS ROM was reduced in 15 patients. Osseous TMJ and UCS changes were both found in 38.5% of the patients. Osseous UCS changes were found more frequently in patients with than without TMJ changes (P = .0003; odds ratio 21.9). No other significant results were found. CONCLUSIONS: The present findings of comorbid osseous changes in patients with obstructive sleep apnea support a possible biomechanical relationship between the TMJ and the UCS.

PET/MR Imaging in Musculoskeletal Disorders.

There is emerging evidence suggesting that PET/MR imaging will have a role in many aspects of musculoskeletal imaging. The synergistic potential of hybrid PET/MR imaging in terms of acquiring anatomic, molecular, and functional data simultaneously seems advantageous in the diagnostic workup, treatment planning and monitoring, and follow-up of patients with musculoskeletal malignancies, and may also prove helpful in assessment of musculoskeletal infectious and inflammatory disorders. The application of more sophisticated MR imaging sequences and PET radiotracers other than FDG in the diagnostic workup and follow-up of patients with musculoskeletal disorders should be explored.

Forensic age estimation from the clavicle using 1.0T MRI--preliminary results.

OBJECTIVES: As forensic age estimations in the living are performed without medical indication, there is a need for the development of non-ionizing methods. This study investigates the use of 1.0T MRI to visualize the ossification status of the medial end of the clavicle. MATERIAL AND METHODS: T2 weighted 3D images were collected from a 1.0T MR system. We prospectively scanned 102 subjects, 47 autopsy cases and 55 living volunteers (12-33 years). Images were scored in blind trials by three observers using a 4-stage system. Observers differed by level of training and radiological expertise. RESULTS: Motion artefacts reduced image resolution in living subjects. However, mean age at stage 4 was significantly different from mean age at stage 2 and 3. The minimum age at stage 4 was 19.8 years. Inter-observer agreement was moderate for autopsy cases and slight for living subjects. By contrasting subjects of "incomplete fusion" (≤ stage 3 on both sides) against "fused" (at least one stage 4), agreement rate rose to moderate (K=0.414) for living subjects. Despite the low agreement rate, no subject younger than 18 years was assessed as having "fused" clavicles. CONCLUSION: At lower image resolution, a 2-stage system increases agreements rates among observers. To further increase accuracy, clavicle staging needs to be performed by trained observers. If available, a 1.0T MR system may be used for age estimation in the living. However, further studies are needed to ensure that the ability to discriminate adults from minors, i.e. 18 years, is maintained.

PET/MRI for Preoperative Planning in Patients with Soft Tissue Sarcoma: A Technical Report of Two Patients.

Clinical positron emission tomography (PET)/magnetic resonance imaging (MRI) acquisition protocols may improve the evaluation of soft tissue sarcomas (STS) prior to surgical planning. We examined two patients with lower extremity STS using a Siemens Biograph mMR PET/MRI scanner and the glucose analogue 18F-fluoro-deoxyglucose (FDG). We investigated clinically relevant tumor volumes and evaluated the relations to skeletal periosteum and nerve bundles. The patient scans suggest that FDG PET/MRI improved the edge detection, and invasion of tumor tissue into important adjacent anatomical structures can be evaluated. FDG PET/MRI also provided additional information compared to conventional Gadolinium enhanced MR imaging. The findings were proven by subsequent pathological examination of the resected tumor tissue. In the future, clinical FDG PET/MRI may be an important modality for preoperative planning, including radiation therapy planning in patients with STS.

Few adverse reactions to metal on metal articulation in total hip arthroplasty in a review study on 358 consecutive cases with 1 to 5 years follow-up.

The aim of the present study was to determine the frequency of adverse reaction to metal on metal total hip arthroplasty using a M2a-38 articulation and a Magnum articulation, (Biomet Warsaw, Indiana).All patients who had received a Metal on Metal bearing prosthesis, in two centres in Copenhagen, were asked to complete a questionnaire about groin pain. Patients with self-reported groin pain, 68/314, underwent a physical examination and had Co and Cr ion levels measured in full blood samples. Fifty patients also had a CT scan performed.The present study found one patient with bilateral arthroplasty, who had an adverse reaction on one side. In addition the study showed that females had higher values of Co and Cr, and that younger patient reported groin pain more often.The conclusion of this study is that the number of adverse reactions is low, despite the time of observation being relatively short, no high frequency of adverse reactions to this prosthesis is expected.

MRI and pathology in persistent postherniotomy pain.

BACKGROUND: Persistent postherniotomy pain impairs everyday life in 5% to 10% of patients. MRI can potentially be useful in the investigation of pathogenic mechanisms and guide surgeons in mesh removal and neurectomy. No study has investigated interobserver agreement or MRI-specific findings in persistent postherniotomy pain. STUDY DESIGN: Thirty-two patients with persistent postherniotomy pain > 1 year after uni- or bilateral groin hernia repair and 6 pain-free postherniotomy controls were MRI scanned, resulting in a total of 32 painful groins, 15 pain-free operated groins, and 29 pain-free unoperated groins scanned. Two blinded observers separately assessed groins using a predefined list of possible MRI pathology and anatomic landmarks. Primary outcomes included interobserver agreement assessed by calculating kappa-coefficients. Secondary outcomes included frequency of MRI pathology in painful groins versus unoperated and pain-free groins. RESULTS: Interobserver agreement was poor, ranging from kappa = 0.24 to 0.55 ("fair" to "moderate") except for "contrast enhancement in groin" (kappa = 0.69, substantial). Pathologic changes in the form of "contrast enhancement in groin," "edema," and "spermatic cord caliber increased" were significantly more often seen in painful versus unoperated groins (p < 0.02). No significant difference was seen when painful and pain-free operated groins were compared (p < 0.05). No pathologic finding was specific or seen in all painful groins. CONCLUSIONS: Interobserver agreement is low and MRI-assessed pathology unspecific for persistent postherniotomy pain. Additional studies are required on interobserver agreement for pathology before MRI can be recommended as guidance and indication for surgical treatment of persistent postherniotomy pain.

MRI quantification of rheumatoid arthritis: current knowledge and future perspectives.

The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detecting and quantifying joint damage in RA. However, radiographs only show late disease manifestations as joint space narrowing and bone erosions, whereas it cannot detect synovitis and bone marrow oedema, i.e., inflammation in the synovium or the bone, which may be visualized by magnetic resonance imaging (MRI) months to years before erosions develop. Furthermore, MRI allows earlier visualization of bone erosions than radiography. In order to allow early treatment initiation and optimal guidance of the therapeutic strategy, there is a need for methods which are capable of early detection of inflammatory joint changes. In this review, we will discuss available data, advantages, limitations and potential future of MRI in RA.

Intra-articular distribution pattern after ultrasound-guided injections in wrist joints of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the distribution of an ultrasound-guided intra-articular (IA) injection in the wrist joint of patients with rheumatoid arthritis (RA). METHODS: An ultrasound-guided IA drug injection into the wrist joint was performed in 17 patients with 1 ml methylprednisolone (40 mg/ml), 0.5 ml Lidocaine (5mg/ml) and 0.15 ml gadolinium (Omniscan 0.5 mmol/ml). The drug solution was placed in the central proximal part of the wrist between the distal radius and the lunate bone. Coronal and axial MRI sequences were performed after the injection to visualize the distribution. Carpal distribution (radio-carpal, inter-carpal, and carpo-metacarpal) as well as radio-ulnar distribution was recorded. Full distribution in one compartment was given the value 1, partial distribution 0.5 and no distribution 0. A sum of the total distribution for all four compartments was calculated and correlated to the clinical parameters and the MRI OMERACT scores. RESULTS: No uniform pattern was seen in the distribution of the contrast. Only two patients had full contrast distribution to all four compartments, and the mean distribution count for all patients was 2.4 (range 0.5-4). The distribution count correlated with the MRI OMERACT synovitis score (r=0.60, p=0.014), but not with the erosions, bonemarrow oedema scores or any clinical parameters. CONCLUSION: The distribution of contrast on MRI showed patient specific and random patterns after IA injections in active RA wrist joints. The degree of distribution increased with the MRI synovitis score, while no association was found with the erosion- and bonemarrow oedema score. These results indicate that a single injection into a standard injection site in the proximal part of the wrist cannot be assumed to distribute--and treat--the whole joint.

Biomarkers of inflammation in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity and radiographic outcome.

OBJECTIVE: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome. METHODS: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions. RESULTS: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03). CONCLUSION: Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.

Clinical outcome and imaging changes after intraarticular (IA) application of etanercept or methylprednisolone in rheumatoid arthritis: magnetic resonance imaging and ultrasound-Doppler show no effect of IA injections in the wrist after 4 weeks.

OBJECTIVE: To assess the magnetic resonance imaging (MRI) and ultrasound (US) changes in the wrist of patients with rheumatoid arthritis (RA) 4 weeks after an US guided intraarticular (IA) injection. METHODS: Contrast enhanced MRI and US-Doppler were performed at baseline and 4 weeks after IA injection of either 40 mg methylprednisolone (n = 12) or 25 mg etanercept (n = 13) in 25 patients with RA taking disease modifying antirheumatic drugs with a therapy-resistant wrist joint. All injections were US guided. RESULTS: There was an improvement in swollen target joint score (p < 0.001), tender target joint score (p < 0.002), and physician visual analog scale score (p < 0.001) after 4 weeks. Baseline MRI synovitis score was mean 5.08 (range 3-9) and was unchanged at followup in the whole group (p = 0.52) and between treatment groups (p = 0.43). MRI edema score (mean 4.46, range 0-29) in the total group was unchanged after 4 weeks (p = 0.13), whereas MRI erosion score increased in the total group from baseline, 17.88 (range 7-40), to 4 weeks, 18.25 (range 7-40) (p < 0.001). Neither US-Doppler color fraction (0.07) nor Resistive Index (RI) (p = 0.36) changed from baseline to 4 week followup. CONCLUSION: In contrast to the clinical evaluation, imaging measures of relevance for the estimation of inflammation, US-Doppler, US RI, MRI synovitis, and bone-marrow edema did not change 4 weeks after a single IA injection of either methylprednisolone or etanercept in the wrist. Within the same period, erosive progression in some patients suggested that joints with active disease may deteriorate within as little as 1 month, and that this development is not arrested by 1 injection. Given the small sample size of our study further studies are required to confirm our results.

Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2.

BACKGROUND: The Pierre Robin sequence (PRS), consisting of cleft palate, micrognathia and glossoptosis, can be seen as part of the phenotype in other Mendelian syndromes--for instance, campomelic dysplasia (CD) which is caused by SOX9 mutations--but the aetiology of non-syndromic PRS has not yet been unravelled. OBJECTIVE: To gain more insight into the aetiology of PRS by studying patients with PRS using genetic and cytogenetic methods. METHODS: 10 unrelated patients with PRS were investigated by chromosome analyses and bacterial artificial chromosome arrays. A balanced translocation was found in one patient, and the breakpoints were mapped with fluorescence in situ hybridisation and Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations, and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out by quantitative real-time PCR. RESULTS: An abnormal balanced karyotype 46,XX, t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and 800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9 and KCNJ2 mRNA expression was observed in patients with PRS. CONCLUSION: Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.

Connective tissue metabolism in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity, bone mineral density, and radiographic outcome.

OBJECTIVE: To assess the applicability of serum concentrations of markers of synovial inflammation, cartilage, and bone metabolism in relation to conventional markers of disease activity, bone mineral density (BMD) of the hand, and radiographic outcome. METHODS: Biochemical markers of collagen tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis (RA) and 21 patients had unclassified polyarthritis. Patients with RA were divided into groups according to the mean disease activity and to magnetic resonance imaging and radiographically detected bone erosions in the hands. RESULTS: Patients with RA had significantly higher serum concentrations of matrix metalloproteinase-3 (MMP-3) at baseline and higher mean concentrations of serum MMP-3 and pyridinoline (Pyd) during the first 6 and 12 months than patients with unclassified polyarthritis. RA patients with persistent disease activity and erosive disease had significantly higher concentrations of serum MMP-3 and Pyd than patients with no disease activity or nonerosive disease. Significant mutual correlations between serum MMP-3 and Pyd and C-reactive protein and erythrocyte sedimentation rate were observed. The mean values of MMP-3 and Pyd correlated significantly to the alpha coefficient of the digital x-ray radiogrammetry (DXR-BMD). CONCLUSION: Serum MMP-3 and Pyd varied according to disease activity, periarticular osteoporosis measured by DXR, and radiographic outcome, and thus appear to supplement the conventional markers of disease activity for monitoring patients with RA.

New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier.

OBJECTIVE: In a 5-year followup study, we investigated the temporal relationship between development of wrist joint erosions as visualized by magnetic resonance imaging (MRI) versus conventional radiography (CR), in patients with rheumatoid arthritis. We also evaluated the risk of erosive progression on CR associated with the presence of MRI erosions. METHODS: In 10 patients with rheumatoid arthritis, MRI and CR of the dominant wrist were performed annually for 5 years. In each image set, each wrist bone (metacarpal bases, carpal bones, radius, and ulna) was assessed for the absence or presence of bone erosions. RESULTS: Nine bones showed radiographic erosions at baseline. Twenty-seven new radiographic erosions developed during the 5-year followup period. Of these 27 new erosions, 21 were detected 1-5 years earlier by MRI than by CR, 3 were simultaneously detected by both methods, 2 were detected 1-2 years later by MRI than by CR, and 1 erosion (radiographically detected at 5-year followup) was not visualized with MRI. MRI detection of new radiographic erosions preceded CR detection by a median of 2 years. In bones with MRI erosions at baseline, the relative risk of radiographic erosions at 5-year followup was 4.5 (95% confidence interval [95% CI] 2.6-7.6), compared with bones without baseline MRI erosions. If bones with baseline radiographic erosions were excluded from the analysis, the relative risk was 4.1 (95% CI 2.2-7.5). CONCLUSION: Most new radiographic bone erosions (78%) were visualized at least 1 year earlier by MRI than by CR. This illustrates that the information on joint destruction provided by CR is considerably delayed compared with that provided by MRI. A significantly increased risk of progression of radiographic erosion in bones with baseline MRI erosions was observed, demonstrating a prognostic value of MRI with respect to long-term radiographic outcome.