Computed tomography and magnetic resonance imaging of unusual causes of ankle pain

Computed tomography and MRI are frequently utilized to evaluate ankle pain that remains unexplained by radiography. The most common causes of ankle pain are related to trauma and the imaging appearances of these entities are well established in the radiologic and orthopedic literature. A smaller percentage is comprised of non‐traumatic disorders. Our goal is to emphasize the value of CT and MRI in recognition of these less common and unusual causes of ankle pain.     

Magnetic resonance imaging of ankle tendons and ligaments: Part I – Anatomy

Magnetic resonance imaging is an excellent technique for imaging the tendons and the ligaments of the ankle. Owing to the advantage of detailed demonstration of soft‐tissue structures and capability for multiplanar demonstration of the ankle ligaments and tendons, MRI has been increasingly used in the evaluation of the ligamentous and the tendon injuries of the ankle. Knowledge of normal anatomy and of MRI appearances are essential to recognize pathological appearances. In this pictorial essay, the first of a three part series, we review the normal MRI appearances of the ankle tendons and ligaments. The anterior, lateral and medial tendon groups, the Achilles tendon and the lateral, the syndesmotic and the medial ligament groups are described and illustrated. Anatomy of the sinus tarsi is also described. Tendon and ligament pathology will be illustrated in the second part of the series, and imaging approach to ankle injuries will be outlined in the final part of this series.     

Magnetic resonance imaging of the ankle: Pathology of the lateral and posterior compartments

Magnetic resonance imaging (MRI) is the gold standard for imaging the tendons and the ligaments of the ankle. MRI combines excellent tissue contrast and accurate anatomic delineation of joint structures. In the first article of this series, we discussed a compartmental approach to the interpretation of ankle pathology focusing on the anterior and medial compartments. This article will complete the MR review of the ankle, with a focus on the lateral and posterior compartments of the ankle.     

MRI in ankle tuberculosis: Review of 14 cases

We reviewed the MR imaging features of ankle tuberculosis and determined the role of MR in its diagnosis. A retrospective analysis of 14 cases of ankle tuberculosis imaged with MRI was performed. Plain radiographs were also reviewed where available, and the imaging characteristics were noted. We also reviewed the medical records in order to assess the impact of the imaging findings on management of these patients. Magnetic resonance imaging is extremely helpful for detection, mapping the extent and resolution of the disease. It can identify cases, enables early institution of antituberculous chemotherapy and might obviate the need for surgery.     

Magnetic resonance imaging of the ankle: Pathology of the anterior and medial compartments

Magnetic resonance imaging (MRI) is the gold standard for imaging the tendons and the ligaments of the ankle. MRI combines excellent tissue contrast and accurate anatomic delineation of joint structures. In this pictorial essay, the first of two parts, we delineate the ankle into anatomic compartments and use this as a template for describing pathology in each compartment.     

Diagnostic imaging of ankle syndesmosis injuries: A general review

Literature on the various techniques for imaging injuries to the ankle syndesmosis to determine the most appropriate imaging modality for diagnosing syndesmosis ligament disruption and instability was reviewed using the following data sources: Pubmed, Google scholar, SportsDiscus, E‐journals and PLOSone. Search terms used were: syndesmosis paired with injury, imaging, radiology, X‐ray, stress X‐ray, arthrography, ultrasound, nuclear medicine scan, CT scan, MRI and arthroscopy. Articles were selected by reading abstracts and the full article if indicated. Further articles were derived from the references of the primary articles. Plain x‐rays of the ankle will detect approximately half on AP view to two‐thirds on mortise view of syndesmosis injuries. Syndesmosis injuries frequently occur in association with tibial or fibular fractures. Intra‐operative stress radiography failed to detect approximately half of instabilities confirmed at arthroscopy. The current benchmark imaging techniques to diagnose syndesmosis injury and diastasis are arthroscopy and high‐power (3T) MRI. Ultrasound is a promising, developing, cost‐effective imaging technique which is yet to reach its full diagnostic potential. CT and nuclear medicine scans have limited roles. MRI (3T) scanning in the plane of the syndesmotic ligaments is the investigation of choice to detect ankle syndesmosis injuries. In the presence of associated injuries requiring surgery, arthroscopic viewing with stress examination is the diagnostic benchmark when available.     

Evaluation of thickness and appearance of anterior talofibular and calcaneofibular ligaments in normal versus abnormal ankles with MRI

Injuries to the lateral ligaments of the ankle are common in medical practice. The most commonly injured ligaments are the anterior talofibular (ATFL) and calcaneofibular (CFL) ligaments. When undertaking MRI evaluation of ankle injuries it is important to understand the normal dimensions, appearance and variations of these ligaments. Twenty‐eight consecutive patients referred for MRI of the ankle underwent bilateral scanning. The thickness of normal and abnormal ATFL and CFL was determined. The mean thickness of the ATFL was 2.19 ± 0.6 mm and the CFL measured 2.13 ± 0.5 mm. One normal ankle had an extremely thin ATFL (0.8 mm) with an otherwise normal appearance, whereas two ankles had an ATFL with a high attachment, both of which were deemed to be normal variants. Nineteen per cent of normal CFLs were noted to consist of a lateral hypointense band with a medial isointense medial band. Two variations of normal ATFL, one normal variant CFL and a measurement of the normal thickness of the ATFL and CFL have been presented in this paper. These variations have not been described previously by other authors. It is envisaged that these findings will assist in the MRI assessment of the lateral ankle ligaments.     

Multiple bilateral spinal nerve root calcifications in Charcot‐Marie‐Tooth disease

We present a patient with Charcot‐Marie‐Tooth disease with multiple bilateral symmetrical cervical nerve root calcifications. To our knowledge, such a finding has not been described in the literature in association with this disease. We propose that multiple bilateral symmetrical spinal nerve root calcifications may be an additional imaging feature, possibly diagnostic, in this hereditary motor and spinal neuropathy.     

Concomitant diminishing magnetization‐transfer effect and increasing choline level in radiation‐induced temporal‐lobe changes

This article reports on the use of both magnetization–transfer (MT) imaging and ¹H‐MR spectroscopy in two cases of bilateral temporal‐lobe changes after radiation therapy for nasopharyngeal carcinoma. In the first case, the following patterns were noted: (i) although the temporal lobes appeared relatively normal on T2‐weighted MR imaging, corresponding MT imaging clearly showed signal abnormalities (decreased MT effect) consistent with alterations in macromolecular structure; and (ii) concomitant strongly elevated choline on ¹H‐MR spectroscopy was observed, and this is associated with metabolic changes in cell membranes. The second case presented similar characteristics. In addition, there was an increased lactate signal and T2 signal changes in keeping with established oedema. Both MT and proton‐spectroscopic findings were consistent with postulated pathophysiological features of radiation injury, but their specificity for this condition remains unclear. Magnetization‐transfer imaging, and possibly ¹H‐MR spectroscopy, might be sensitive techniques for the early detection of late radiation injury.     

Geometric accuracy in three‐dimensional coordinates of Leksell stereotactic skull frame with wide‐bore 1.5‐T MRI compared with conventional 1.5‐T MRI

The use of 1.5‐tesla (T) magnetic resonance (MR) imaging with a wide and simultaneously short bore enhances patient comfort compared with traditional 1.5‐T MR imaging and is becoming increasingly available in stereotactic radiosurgery treatment planning. However, the geometric accuracy seems unavoidably worse in wide‐bore MR imaging than in conventional MR imaging. We assessed the geometric distortion of the stereotactic image attached on a Leksell skull frame in conventional and wide‐bore 1.5‐T MR imaging. Two kinds of acrylic phantoms were placed on the skull frame and were scanned using computed tomography (CT) and conventional and wide‐bore 1.5‐T MR imaging. The three‐dimensional coordinates on both MR imaging were compared with those on CT. Deviations of measured coordinates at selected points (x = 50, 100, 150 mm; y = 50, 100, 150 mm) were indicated on different axial planes (z = 50, 75, 100, 125, 150 mm). The differences of coordinates were less than 1.0 mm in the entire treatable area for conventional MR imaging. With the large bore system, the differences of the coordinates were less than 1.0 mm around the center but substantially exceeded 1.0 mm in the peripheral regions. Further study is needed to increase the geometric accuracy of wide‐bore MR imaging for stereotactic radiosurgery treatment planning.     

Inter‐ and intra‐fraction motion during radiation therapy to the whole breast in the supine position: A systematic review

Inter‐ and intra‐fraction motion during radiation therapy for breast cancer has been a widely researched topic. Recently, however, with the emergence of new technologies and techniques such as intensity modulated radiation therapy (IMRT), field in field, volumetric modulated arc therapy (VMAT), tomotherapy and partial breast irradiation (PBI), the magnitude of this movement has become more important. The aim of this study is to provide a comprehensive summary of the literature relating to the magnitude of motion during radiation therapy for a breast cancer patient. A systematic review of the literature was conducted using Medline, Cinhal, Embase, Scopus and Web of Science. Studies included were limited to women having radical radiation therapy to the whole breast in the supine position. Studies needed to report quantitatively on the magnitude of inter‐ and intra‐fraction motion using electronic portal imaging, port films or kilovoltage imaging techniques. Eighteen articles fitted the selection criteria. The averages of random and systematic error for inter‐ and intra‐fraction movement were reported using central lung distance, central irradiated width, central beam edge to skin distance and cranio‐caudal distance measurements, or isocentric matching techniques. Inter‐fraction motion was consistently larger than intra‐fraction motion but, on average, within a 5 mm tolerance. There were, though, large maximum inter‐ and intra‐fraction variations observed in the measurements of individual patients, which indicate the need for daily inter‐ and intra‐ fraction motion management before implementing IMRT, VMAT, tomotherapy or PBI techniques.     

In vivo subcellular imaging of tumors in mouse models using a fluorophore‐conjugated anti‐carcinoembryonic antigen antibody in two‐photon excitation microscopy

Recently, there has been growing interest in applying fluorescence imaging techniques to the study of various disease processes and complex biological phenomena in vivo. To apply these methods to clinical settings, several groups have developed protocols for fluorescence imaging using antibodies against tumor markers conjugated to fluorescent substances. Although these probes have been useful in macroscopic imaging, the specificity and sensitivity of these methods must be improved to enable them to detect micro‐lesions in the early phases of cancer, resulting in better treatment outcomes. To establish a sensitive and highly specific imaging method, we used a fluorophore‐conjugated anti‐carcinoembryonic antigen (CEA) antibody to perform macroscopic and microscopic in vivo imaging of inoculated cancer cells expressing GFP with or without CEA. Macroscopic imaging by fluorescence zoom microscopy revealed that bio‐conjugation of Alexa Fluor 594 to the anti‐CEA antibody allowed visualization of tumor mass consisting of CEA‐expressing human cancer cells, but the background levels were unacceptably high. In contrast, microscopic imaging using a two‐photon excitation microscope and the same fluorescent antibody resulted in subcellular‐resolution imaging that was more specific and sensitive than conventional imaging using a fluorescence zoom microscope. These results suggest that two‐photon excitation microscopy in conjunction with fluorophore‐conjugated antibodies could be widely adapted to detection of cancer‐specific cell‐surface molecules, both in cancer research and in clinical applications.     

T1‐weighted fluid‐attenuated inversion recovery and T1‐weighted fast spin‐echo contrast‐enhanced imaging: A comparison in 20 patients with brain lesions

T1‐weighted fluid‐attenuated inversion recovery (FLAIR) sequence is a relatively new pulse sequence for intracranial MR imaging. This study was performed to compare the image quality of T1‐weighted FLAIR with the T1‐weighted FSE sequence. Twenty patients with brain lesions underwent T1‐weighted fast spin‐echo (FSE) and T1‐weighted FLAIR during the same imaging session. Four quantitative and three qualitative criteria were used to compare the two sequences after contrast. Two of four quantitative criteria pertained to lesion characteristics: lesion to white matter (WM) contrast‐to‐noise ratio (CNR) and lesion to cerebrospinal fluid (CSF) CNR, and two related to signals from normal tissue: grey matter to WM CNR and WM to CSF CNR. The three qualitative criteria were conspicuousness of the lesion, the presence of image artefacts and the overall image contrast. Both T1‐weighted FSE and FLAIR images were effective in demonstrating lesions. Image contrast was superior in T1‐weighted FLAIR images with significantly improved grey matter‐WM CNRs and CSF‐WM CNRs. The overall image contrast was judged to be superior on T1‐weighted FLAIR images compared with T1‐weighted FSE images by all neuroradiologists. Two of three reviewers considered that the FLAIR images had slightly increased imaging artefacts that, however, did not interfere with image interpretation. T1‐weighted FLAIR imaging provides improved lesion‐to‐background and grey to WM contrast‐to‐noise ratios. Superior conspicuity of lesions and overall image contrast is obtained in comparable acquisition times. These indicate an important role for T1‐weighted FLAIR in intracranial imaging and highlight its advantage over the more widely practiced T1‐weighted FSE sequence.     

Fluorescence‐based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin‐type tumor‐associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF‐associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio‐imaging index for the probe. The nanobeacon exhibited specificity for TF‐associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio‐imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.     

μ‐Calpain regulates caspase‐dependent and apoptosis inducing factor‐mediated caspase‐independent apoptotic pathways in cisplatin‐induced apoptosis

Cisplatin, an effective anticancer agent, can induce tumor cell apoptosis via caspase‐dependent and‐independent pathways. However, the precise mechanism that regulates the pathways remains unclear. In this study, we showed that μ‐calpain mediated both caspase‐dependent and‐independent pathways during cisplatin‐induced apoptosis in human lung adenocarcinoma cells. After cisplatin treatment, calpain activation, as measured by a fluorescent substrate, was an early event, taking place well before apoptosis inducing factor (AIF) release and caspase‐9/‐3 activation. Confocal imaging of cells transfected with AIF‐GFP demonstrated that AIF release occurred about 9 hr after cisplatin treatment. The increase of μ‐calpain activity proved to be a crucial event in the apoptotic machinery, as demonstrated by the significant protection of cell death in samples suppressed the endogenous μ‐calpain expression level, as well as cotreated with the calpain inhibitors, calpeptin and PD150606. Inhibition of μ‐calpain not only significantly reduced caspase‐9/‐3 activities but also completely blocked AIF redistribution. Our study also showed that endogenous mitochondrial μ‐calpain could directly induce the truncation and release of AIF, while caspases and cathepsins were not necessary for this process. In conclusion, the study demonstrated that activation of μ‐calpain played an essential role in regulating both caspase‐dependent and AIF‐mediated caspase‐independent apoptotic pathways in cisplatin‐induced apoptosis. © 2009 UICC     

Unusual extra‐axial central nervous system involvement of non‐Hodgkin’s lymphoma: Magnetic resonance imaging

The MR imaging findings in a patient with non‐Hodgkin’s lymphoma with unusual involvement of the sella, pituitary stalk and left parasellar region are reported here. On the basis of the MR imaging findings, the initial differential diagnosis included invasive pituitary adenoma, a granulomatous lesion and en plaque meningioma. Trans‐sphenoidal biopsy of the sellar mass showed chronic inflammatory changes and the patient was initially treated for tuberculosis. Because follow‐up imaging showed the lesion to be progressive, a biopsy was done of an enlarged right inguinal lymph node. This revealed non‐Hodgkin’s lymphoma.     

FDG‐PET/CT is a pivotal imaging modality to diagnose rare intravascular large B‐cell lymphoma: case report and review of literature

Intravascular large B‐cell lymphoma (IVLBCL) remains a diagnostic challenge, because of non‐specific findings on clinical, laboratory, and imaging studies. We present a case in which 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET)/computed tomography was particularly useful to suspect the diagnosis, to detect unexpected locations, to guide contributive biopsy, and to assess the response to treatment. In case of initial negative results, FDG‐PET should be repeated in the course of clinical evolution. In the presence of neurological or hormonal symptoms without brain magnetic resonance imaging abnormality, FDG‐PET brain slices could depict additional pituitary and/or brain hypermetabolisms. We discuss the potential interests of FDG‐PET in IVLBCL by a literature review. Copyright © 2014 John Wiley & Sons, Ltd.     

儿童马蹄足外架矫正后踝关节功能的影响因素分析

目的外固定架治疗儿童马蹄足,可矫正严重、僵硬的畸形并已得到大量的临床验证。但畸形矫正后踝关节活动范围 (range of motion,ROM) 如何,报道较少,存在哪些影响因素尚不明确。方法对外固定架矫正后的踝关节进行影像学测量,随访时踝关节最大背屈和最大跖屈时的胫跟角变化值认定为 ROM,并以 20°为分界,标记为优和差,通过多因素分析,评价不同变量对治疗结果的影响。设定可能影响结果的自变量包括:手术时年龄、发病原因、有无手术史、畸形 Dimeglio 评分、外固定架固定时长、术中是否做跟腱切断术 (tenotomy of achcilleus tendon,TAT)、随访时间。结果 2015 年 7 月至 2019 年 7 月,本院小儿骨科共 42 例 (46 足),符合试验设计,纳入本研究。至末次随访,经影像学验证,踝关节 ROM 20 例优 (43.5%),26 例差 (56.5%)。单因素分析结果显示,既往患足是否有手术史 (χ²=8.248,P=0.004)、术中是否 TAT (χ²=6.083,P=0.014)、不同病因对结果的影响差异有统计学意义 (χ²=11.944,P=0.001)。而多因素分析结果显示,仅病因分类 (先天或后天畸形) 与活动度结果的关联差异有统计学意义 (P=0.021),与先天性畸形相比,后天性畸形患足活动度好的可能性是前者的 27 倍。结论外固定架是治疗儿童马蹄内翻足的有效手段,但并非所有患儿均可获得良好的关节功能,以影像学方法对踝关节活动度进行评估,在各种因素中,发病原因对活动度结果产生影响,先天性畸形患足活动度更差。     

Targeting IL‐13Rα2 in human pancreatic ductal adenocarcinoma with combination therapy of IL‐13‐PE and gemcitabine

Pancreatic cancer is an aggressive disease with only limited therapeutic options available. We have identified that 71% pancreatic ductal adenocarcinoma (PDA) express high levels of IL‐13Rα2, a high‐affinity receptor for IL‐13. To target IL‐13Rα2, we have developed a recombinant immunotoxin, which is a fusion of IL‐13 and Pseudomonas exotoxin (IL‐13‐PE). Since IL‐13‐PE and a commonly used cytotoxic drug gemcitabine act by a different mechanism, we hypothesized that they synergize in mediating antitumor response. Both IL‐13‐PE and gemcitabine‐mediated cytotoxicity to two pancreatic cancer cell lines and when combined synergistic cytotoxicity was observed. This synergism was also demonstrated in vivo in an orthotopic mouse model of human PDA. IL‐13‐PE and gemcitabine showed complete eradiation of tumors as assessed by whole body imaging of GFP‐transfected tumors in 57% of mice in an early cancer model resulting into prolongation of survival. In contrast, monotherapy with either agent did not produce complete eradiation, but tumor volumes were significantly decreased. In advanced PDA model, combination therapy also produced dramatic reduction in tumor growth and enhanced survival compared to animals treated with either agent alone. When IL‐13Rα2 was knocked‐down by RNAi prior to tumor implantation, IL‐13‐PE and gemcitabine did not synergize indicating that IL‐13Rα2 is essential. Mechanistically, gemcitabine increased IL‐13Rα2 expression in vitro and in vivo, which resulted in a synergism of combination therapy. Interestingly, PDA cancer stem cells were resistant to gemcitabine, but not to IL‐13‐PE. These results suggest that combination therapy with IL‐13‐PE and gemcitabine may be a useful strategy for PDA therapy.     

Cerebral amyloid angiopathy: Review of clinico‐radiological features and mimics

Cerebral amyloid angiopathy (CAA) is an important cause of lobar intracerebral haemorrhage (ICH) in the elderly, but has other clinico‐radiological manifestations. In the last two decades, certain magnetic resonance imaging (MRI) sequences, namely gradient‐recalled echo imaging and the newer and more sensitive susceptibility‐weighted imaging, have been utilised to detect susceptibility‐sensitive lesions such as cerebral microbleeds and cortical superficial siderosis. These can be utilised sensitively and specifically by the Modified Boston Criteria to make a diagnosis of CAA without the need for ‘gold‐standard’ histopathology from biopsy. However, recently, other promising MRI biomarkers of CAA have been described which may further increase precision of radiological diagnosis, namely chronic white matter ischaemia, cerebral microinfarcts and lobar lacunes, cortical atrophy, and increased dilated perivascular spaces in the centrum semiovale. However, the radiological manifestations of CAA, as well as their clinical correlates, may have other aetiologies and mimics. It is important for the radiologist to be aware of these clinico‐radiological features and mimics to accurately diagnose CAA. This is increasingly important in a patient demographic that has a high prevalence for use of antiplatelet and antithrombotic medications for other comorbidities which inherently carries an increased risk of ICH in patients with CAA.