A. Water Exchange 2326 B. Proton Exchange 2327 C. Electronic Relaxation 2327 D. Relaxivity 2331 E. Outerand Second-Sphere Relaxivity 2334 F. Methods of Improving Relaxivity 2336 V. Macromolecular Conjugates 2336 A. Introduction 2336 B. General Conjugation Methods 2336 C. Synthetic Linear Polymers 2336 D. Synthetic Dendrimer-Based Agents 2338 E. Naturally Occurring Polymers (Proteins, Polysaccharides, and Nucleic Acids) 2339

https://mriquestions.com/uploads/3/4/5/7/34572113/lauffer_1999_review.pdf

Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications

Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.

https://ard.bmj.com/content/annrheumdis/68/6/777.full.pdf

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection

TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases

https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.2287

TNF‐mediated inflammatory disease

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

/pdf/asia-pacific-clinical-practice-guidelines-on-the-management-3qdf1cp1jm.pdf

Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

https://www.oarsijournal.com/article/S1063-4584(03)00291-7/pdf

Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis

Objective To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS). Patients and methods Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. Results Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. Conclusion The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780380407

Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis

PURPOSE: To determine the safety, pharmacokinetics, and magnetic resonance (MR) imaging results of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) as a contrast agent for use in hepatobiliary MR imaging. MATERIALS AND METHODS: Gd-EOB-DTPA was tested at doses of 10, 25, 50, and 100 mumol per kilogram of body weight. Results of laboratory tests, clinical measurements, and pharmacokinetic data were obtained in 44 healthy volunteers in a double-blind, randomized, placebo-controlled design. MR images were obtained in another 16 healthy volunteers before and up to 6 hours after fast intravenous administration of Gd-EOB-DTPA. RESULTS: Gd-EOB-DTPA was well tolerated, with no important side effects or changes in laboratory parameters. Homogeneous enhancement of liver parenchyma was observed immediately after injection of the contrast agent. Peak liver signal intensity was noted 20 minutes after injection, followed by plateaulike enhancement over about 2 hours. The common bile duct was hype...

Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging.

Objective. To evaluate the new magnetic resonance imaging (MRI) method of dynamic MRI with fast imaging in the diagnosis of sacroiliitis among patients with spondylarthropathy.

Methods. Fifteen patients with a history of inflammatory back pain without radiographic evidence of grade II or greater sacroiliitis (group 1), 25 patients with definite ankylosing spondylitis (group 2), and 12 patients with noninflammatory spinal pain (controls) (group 3) were examined. Dynamic MRI with fast imaging was performed after intravenous bolus injection of the contrast agent gadolinium—diethylenetriamine pentaacetic acid. The degree of enhancement was graded as representing acute sacroiliitis, latent sacroiliitis, or no sacroiliitis.

Results. Acute sacroiliitis was detected in 22 of 30 sacroiliac (SI) joints in group 1 patients and in 27 of 50 SI joints in group 2 patients; latent sacroiliitis was seen in 25 of 80 SI joints in patients from groups 1 and 2. No group 3 patient was found to have sacroiliitis.

Conclusion. Early sacroiliitis can be demonstrated by dynamic MRI in spondylarthropathy patients in whom abnormalities are not revealed by conventional radiography.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780370709

Use of dynamic magnetic resonance imaging with fast imaging in the detection of early and advanced sacroiliitis in spondylarthropathy patients

Objective Patients with axial spondylarthritis (SpA) who have structural changes in the sacroiliac joints and/or the spine have been classified as having ankylosing spondylitis (AS), while those without such changes are now classified as having nonradiographic axial SpA (nr-axSpA). The differentiating features are incompletely understood. Methods Data from 100 consecutive patients with axial SpA not treated with tumor necrosis factor antagonists were compared clinically and with laboratory parameters, spinal radiographs, and magnetic resonance imaging (MRI) of the spine. Standardized clinical assessment tools were used to assess health status. Results AS was diagnosed in 56 patients and nr-axSpA in 44 patients. Signs of inflammation were significantly higher in patients with AS than in patients with nr-axSpA, with a median C-reactive protein level of 8.0 versus 3.8 mg/liter, a median Ankylosing Spondylitis Disease Activity Score of 2.2 versus 2.8, respectively, and a median amount of spinal inflammatory lesions on MRI of 2.0 versus 0.0, respectively. Significant differences between these 2 groups were seen in sex (76.8% male AS patients versus 31.8% male nr-axSpA patients). Clinical variables did not differ between patients with AS and nr-axSpA (Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life questionnaire, Short Form 36 health survey). Conclusion Patients with nr-axSpA were characterized by the low proportion of male patients and the low burden of inflammation compared to patients with AS. While both groups did not differ regarding health status, disease activity, and physical function, they did differ in signs of inflammation; all were higher in patients with AS. Since many patients with nr-axSpA had not developed structural changes after years of symptoms, we propose that those patients should not be regarded as having preradiographic AS but rather as having nr-axSpA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.21688

Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis?

Objective: To carry out a prospective two year follow up study comparing conventional radiography, three-phase bone scintigraphy, ultrasonography (US), and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examination in detecting early arthritis. The aim of the follow up study was to monitor the course of erosions during treatment with disease modifying antirheumatic drugs by different modalities and to determine whether the radiographically occult changes like erosive bone lesions of the finger joints detected by MRI and US in the initial study would show up on conventional radiographs two years later. Additionally, to study the course of soft tissue lesions depicted in the initial study in comparison with the clinical findings. 

Methods: The metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (14 joints) of the clinically more severely affected hand (soft tissue swelling and joint tenderness) as determined in the initial study of 49 patients with various forms of arthritis were examined twice. The patients had initially been divided into two groups. The follow up group I included 28 subjects (392 joints) without radiographic signs of destructive arthritis (Larsen grades 0–1) of the investigated hand and wrist, and group II (control group) included 21 patients (294 joints) with radiographs showing erosions (Larsen grade 2) of the investigated hand or wrist, or both, at the initial examination. 

Results: (1) Radiography at the two year follow up detected only two erosions (two patients) in group I and 10 (nine patients) additional erosions in group II. Initial MRI had already detected both erosions in group I and seven (seven patients) of the 10 erosions in group II. Initial US had depicted one erosion in group I and four of the 10 erosions in group II. (2) In contrast with conventional radiography, 3D MRI and US demonstrated an increase in erosions in comparison with the initial investigation. (3) The abnormal findings detected by scintigraphy were decreased at the two year follow up. (4) Both groups showed a marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI and US. (5) There was a striking discrepancy between the decrease in the soft tissue lesions as demonstrated by clinical findings, MRI, and US, and the significant increase in erosive bone lesions, which were primarily evident at MRI and US. 

Conclusions: Despite clinical improvement and a regression of inflammatory soft tissue lesions, erosive bone lesions were increased at the two year follow up, which were more pronounced with 3D MRI and less pronounced with US. The results of our study suggest that owing to the inadequate depiction of erosions and soft tissue lesions, conventional radiography alone has limitations in the intermediate term follow up of treatment. US has a high sensitivity for depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive in differentiating minute erosions.

https://ard.bmj.com/content/annrheumdis/61/10/895.full.pdf

M. Bollow

Papers

Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis

Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging.

Use of dynamic magnetic resonance imaging with fast imaging in the detection of early and advanced sacroiliitis in spondylarthropathy patients

Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis?

Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints