Whole brain and corpus callosum diffusion tensor metrics: How do they correlate with visual and verbal memory performance in chronic traumatic brain injury.

This research investigates the chronic effect of moderate to severe traumatic brain injury on brain white matter integrity, as reflected by diffusion tensor imaging metrics, and the assessment of their correlation to neuropsychological response. Thirteen male participants with traumatic brain injury (8.4 years average post-injury time) were compared to a matched group of neurologically healthy controls. None of the traumatic brain injury subjects had received post-acute neurocognitive and/or neuropsychological rehabilitation. Between-group comparison of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity was performed for the whole brain and corpus callosum. An extensive battery of visual and verbal memory tasks was employed for the comparative assessment of neurocognitive performance. Between-group and within-group performance differences were correlated with fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of corpus callosum. Significant changes in global fractional anisotropy, mean diffusivity, and radial diffusivity were associated with traumatic brain injury. Visual memory capacity was reduced in traumatic brain injury, and this deficit was correlated to white matter integrity loss at the corpus callosum. Participants with traumatic brain injury underperformed controls in verbal memory as well, but no correlation with corpus callosum diffusion tensor imaging properties was established. Between-group performance difference was correlated with corpus callosum diffusion metrics in several tasks. Significant correlations were found between corpus callosum diffusion tensor imaging metrics and neuropsychological response within the traumatic brain injury group. Changes in whole brain and corpus callosum diffusion tensor metrics inflicted by moderate to severe traumatic brain injury are still evident several years post-injury and relate to neurocognitive impairment, while loss of white matter integrity seems to correlate with episodic and working memory impairment.

Penile Mondor's disease in a patient treated with radical chemoradiation for anal cancer.

Penile Mondor's disease is a rare condition characterized by sclerosing thrombophlebitis of the superficial dorsal penile vein. Usually its causes are benign, but it is also evident in cancer patients. We report the case of a 62-year-old man with a cT4 anal cancer (infiltration of corpora spongiosa and penile bulb), associated with extensive loco-regional lymphadenopathy, who developed painful lumps in the midline of the anterior penile surface while receiving radical chemoradiotherapy. Physical examination revealed two palpable cord-like swellings located 2 cm from the pubic symphysis. Color Doppler ultrasound established the diagnosis of Mondor's disease. The patient was successfully managed with non-steroidal anti-inflammatory drugs. The causative factors were pelvic malignancy and radiotherapy. The diagnosis was challenging since Mondor's disease is a rare condition and the differential diagnosis included malignancy progression. This is the first case report describing penile Mondor's disease in a patient with anal cancer under chemoradiotherapy.

Assessing the Relationship between Neurocognitive Performance and Brain Volume in Chronic Moderate-Severe Traumatic Brain Injury.

OBJECTIVES: Characterize the scale and pattern of long-term atrophy in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in chronic moderate-severe traumatic brain injury (TBI) and its relationship to neurocognitive outcomes. PARTICIPANTS: The TBI group consisted of 17 males with primary diagnosis of moderate-severe closed head injury. Participants had not received any systematic, post-acute rehabilitation and were recruited on average 8.36 years post-injury. The control group consisted of 15 males matched on age and education. MAIN MEASURES: Neurocognitive battery included widely used tests of verbal memory, visual memory, executive functioning, and attention/organization. GM, WM, and CSF volumes were calculated from segmented T1-weighted anatomical MR images. Voxel-based morphometry was employed to identify brain regions with differences in GM and WM between TBI and control groups. RESULTS: Chronic TBI results in significant neurocognitive impairments, and significant loss of GM and WM volume, and significant increase in CSF volume. Brain atrophy is not widespread, but it is rather distributed in a fronto-thalamic network. The extent of volume loss is predictive of performance on the neurocognitive tests. CONCLUSION: Significant brain atrophy and associated neurocognitive impairments during the chronic stages of TBI support the notion that TBI results in a chronic condition with lifelong implications.

A novel, general-purpose, MR-compatible, manually actuated robotic manipulation system for minimally invasive interventions under direct MRI guidance.

BACKGROUND: Performing minimally invasive interventions under direct MRI guidance offers significant advantages. Required accessibility to the patient inside the MRI scanner is fairly limited, and employment of robotic assistance has been proposed. The development of MR-compatible robotic systems entails engineering challenges related to geometric constraints and the magnetic nature of the scanning environment. METHODS: A novel, general-purpose, MR-compatible robotic manipulation system has been developed for the performance of minimally invasive interventions inside a cylindrical scanner under direct MRI guidance. The system is endowed with five degrees of freedom (DOF), is characterized by a unique kinematics structure and is manually actuated. RESULTS: The prototype system was shown to exhibit the required MR-compatibility characteristics and a task-space positioning ability of approximately 5 mm. Needle targeting testing demonstrated a 93% success rate in acquiring a 5 mm spherical target. Phantom testing was performed inside a 3 T scanner and results are reported for an experimental study simulating MRI-guided, manipulator-assisted, MR arthrography. CONCLUSIONS: Robotic assistance provided by the developed manipulator may effectively facilitate the performance of various MRI-guided, minimally invasive interventions inside a cylindrical scanner.

An approach for preoperative planning and performance of MR-guided interventions demonstrated with a manual manipulator in a 1.5T MRI scanner.

PURPOSE: The aim of this work was to develop and test a general methodology for the planning and performance of robot-assisted, MR-guided interventions. This methodology also includes the employment of software tools with appropriately tailored routines to effectively exploit the capabilities of MRI and address the relevant spatial limitations. METHODS: The described methodology consists of: (1) patient-customized feasibility study that focuses on the geometric limitations imposed by the gantry, the robotic hardware, and interventional tools, as well as the patient; (2) stereotactic preoperative planning for initial positioning of the manipulator and alignment of its end-effector with a selected target; and (3) real-time, intraoperative tool tracking and monitoring of the actual intervention execution. Testing was performed inside a standard 1.5T MRI scanner in which the MR-compatible manipulator is deployed to provide the required access. RESULTS: A volunteer imaging study demonstrates the application of the feasibility stage. A phantom study on needle targeting is also presented, demonstrating the applicability and effectiveness of the proposed preoperative and intraoperative stages of the methodology. For this purpose, a manually actuated, MR-compatible robotic manipulation system was used to accurately acquire a prescribed target through alternative approaching paths. CONCLUSIONS: The methodology presented and experimentally examined allows the effective performance of MR-guided interventions. It is suitable for, but not restricted to, needle-targeting applications assisted by a robotic manipulation system, which can be deployed inside a cylindrical scanner to provide the required access to the patient facilitating real-time guidance and monitoring.

Effect of posture change on the geometric features of the healthy carotid bifurcation.

Segmented cross-sectional MRI images were used to construct 3-D virtual models of the carotid bifurcation in ten healthy volunteers. Geometric features, such as bifurcation angle, internal carotid artery (ICA) angle, planarity angle, asymmetry angle, tortuosity, curvature, bifurcation area ratio, ICA/common carotid artery (CCA), external carotid artery (ECA)/CCA, and ECA/ICA diameter ratios, were calculated for both carotids in two head postures: 1) the supine neutral position; and 2) the prone sleeping position with head rotation to the right ( ∼ 80°). The results obtained have shown that head rotation causes 1) significant variations in bifurcation angle [32% mean increase for the right carotid (RC) and 21% mean decrease for the left carotid (LC)] and internal carotid artery angle (97% mean increase for the RC, 43% mean decrease for the LC); 2) a slight increase in planarity and asymmetry angles for both RC and LC; 3) minor and variable curvature changes for the CCA and for the branches; 4) slight tortuosity changes for the braches but not for the CCA; and 5) unsubstantial alterations in area and diameter ratios (percentage changes %). The significant geometric changes observed in most subjects with head posture may also cause significant changes in bifurcation hemodynamics and warrant future investigation of the hemodynamic parameters related to the development of atherosclerotic disease such as low oscillating wall shear stress and particle residence times.

Uses and limitations of serum ferritin, magnetic resonance imaging T2 and T2* in the diagnosis of iron overload and in the ferrikinetics of normalization of the iron stores in thalassemia using the International Committee on Chelation deferiprone/deferoxamine combination protocol.

Excess cardiac iron deposition leads to congestive cardiac failure and accounts for more than 70% of deaths in thalassemia major patients. In three separate studies involving 145 thalassemia patients, serum ferritin and magnetic resonance imaging (MRI) relaxation times T2 and T2* have been compared for assessing iron load levels during chelation treatment. In two studies, variable levels of cardiac iron load have been detected by T2 and T2* in patients treated with deferoxamine (DFO), which, however, were unrelated to serum ferritin. In most cases, similar range levels from normal to severe cardiac iron load could be identified by both the T2 and T2* methods. However, in a few cases there were substantial differences in the levels detected between the two methods. In the third study, the ferrikinetics of the normalization of the iron stores during the International Committee on Chelation (ICOC) deferiprone (L1)/DFO combination protocol was followed up using T2 and T2* and serum ferritin. Iron deposits were found not to be proportionally distributed between the liver and the heart or uniformly distributed within each organ. Iron mobilization in each patient varied and iron deposits in each organ were cleared at different rates. Despite some limitations, the application of the MRI relaxation times T2 and T2* offers the best diagnostic methods for iron overload estimations in most organs and especially the heart. These MRI methods and serum ferritin could also be used for the ferrikinetics of iron mobilization and removal during chelation therapy and the normalization of the iron stores during the ICOC L1/DFO combination protocol. There is a need to standardize the two MRI relaxation times T2 and T2* methods and identify the factors causing the differences between them.

Regional migratory osteoporosis in the knee: MRI findings in 22 patients and review of the literature.

OBJECTIVE: Acute non-traumatic bone marrow edema (BME) in the knee is a common clinical problem. The aim of the present study is to present the MR imaging findings of the uncommon transient migratory pattern of this syndrome. MATERIALS AND METHODS: Twenty-two patients (21 men, 1 woman, age range 35-73 years, mean 49.4+/-7.6) who presented with pain in the knee joint (ranging from 2 weeks to 6 months) and BME in the MR imaging examination, were included in the study. In all cases, the knee joint BME was either preceded or followed by another site of BME in the same or another joint. All patients were studied with plain X-rays and MR imaging at presentation and with MR imaging after resolution of symptoms. RESULTS: The eight patients with initial involvement in the knee showed migration either intra-articularly (5), or/and in the contralateral knee (2) and only 1 case showed migration to the ipsilateral hip joint. In two patients the BME shifted from the hip first to the foot and then to the knee. The median migration period was 4 months for the second involvement in all patients and 3 months for the third involvement (10 patients). CONCLUSIONS: The present study reports the largest series of patients with regional migratory osteoporosis involving the knee. In most of the cases, shifting of BME remains in the joint or moves to the contralateral knee. In only one case the BME shifted from the knee elsewhere. All lesions were transient.

Long term comparative studies in thalassemia patients treated with deferoxamine or a deferoxamine/deferiprone combination. Identification of effective chelation therapy protocols.

For the past 2-6 years, two groups of thalassemia patients, one of 16 patients on deferoxamine (DFO) monotherapy (35-80 mg/kg, 2-5 days/week) and the other group comprising 19 patients on a deferiprone (L1) and DFO combination therapy (L1 75-100 mg/kg/day and DFO 30-60 mg/kg, 1-5 days/week), have been studied and compared before and after the introduction of the combination therapy. The patients on the combination therapy were mainly those not complying or experiencing toxicity with DFO. The effects of chelation therapy on iron load was monitored using regular serum ferritin measurements and also magnetic resonance imaging (MRI) T2* relaxation time measurements at the end of the study. In both groups, cardiac MRI T2* levels were within the normal range (>19 ms) in more than 75% of the patients. There was a substantial improvement in serum ferritin levels and normalization of the MRI T2* levels of the liver in many cases treated with the combination therapy at effective doses by comparison to the DFO group, where the serum ferritin and MRI T2* levels were largely unchanged. It would appear that the major overall determining factor in the rapid clearance of excess iron in thalassemia patients and the maintenance of normal iron stores is the selection and implementation of effective chelation dose protocols. The International Committee on Chelation (ICOC) combination protocol L1 (80-110 mg/kg/day)/DFO (40-60 mg/kg at least 3 days per week) and to a lesser extent, DFO monotherapy at about 50 mg/kg/day, 5 days/week, appears to achieve this goal.

Low serum ferritin levels are misleading for detecting cardiac iron overload and increase the risk of cardiomyopathy in thalassemia patients. The importance of cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*.

The incidence of cardiomyopathy was monitored in a 6-year follow-up study involving 56 transfused thalassemia patients treated with deferoxamine (DFO), deferiprone (L1) or their combination. During this period, five female patients on regular subcutaneous or intravenous DFO presented with cardiac complications. Three patients suffered congestive heart failure and the other two arrhythmias. Four of the five patients maintained serum ferritin levels of about 1 mg/L or below and the fifth about 1.5 mg/L for several years prior to the cardiomyopathy. Cardiac magnetic resonance imaging (MRI) T2* and T2 was performed in four patients after the cardiomyopathy, identifying the presence of moderate-to-heavy siderosis. The treatment of the five patients has since changed, involving mainly the use of L1. Low serum ferritin levels appear to be misleading for detecting cardiac iron overload and this may increase the risk of cardiomyopathy. The MRI T2 and T2* relaxation time measurements are a more accurate method of detecting cardiac iron overload. Chelation therapy using L1 or appropriate L1/DFO combinations can reduce cardiac iron overload and the mortality rate in thalassemia patients.

Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations.

Effective new therapies and mechanisms have been developed for the targeting and prevention of iron overload and toxicity in thalassaemia and idiopathic haemochromatosis patients. A new era in the development of chelating drugs began with the introduction of deferiprone or L1, which as a monotherapy or in combination with deferoxamine can be used universally for effective chelation treatments, rapid iron removal, maintenance of low iron stores and prevention of heart and other organ damage caused by iron overload. Several experimental iron chelators such as deferasirox (4-[3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) or ICL670, deferitrin (4,5-dihydro-2- (2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and starch deferoxamine polymers have reached different stages of clinical development. The lipophilic ICL670, which can only be administered once daily is generally ineffective in causing negative iron balance but is effective in reducing liver iron. It is suspected that it may increase iron absorption and the redistribution of iron from the liver to the heart and other organs. The experimental iron chelators do not appear to have significant advantages in efficacy and toxicity by comparison to deferiprone, deferoxamine or their combination. However, the prospect of combination therapies using deferiprone, deferoxamine and new chelators will provide new mechanisms of chelator interactions, which may lead to higher efficacy and lower toxicity by comparison to monotherapies. A major disadvantage of the experimental chelators is that even if they are approved for clinical use, they are unlikely to be as inexpensive as deferiprone and become available to the vast majority of thalassaemia patients, who live in developing countries.

Complementary role of helical CT cholangiography to MR cholangiography in the evaluation of biliary function and kinetics.

To explore the potential role of computed tomographic cholangiography (CTC) in relation to magnetic resonance cholangiography (MRC) in cases in which knowledge of biliary kinetics and functional information are important for therapeutic decisions, 31 patients (14 men and 17 women) underwent MRC followed by CTC. We examined nine post-cholecystectomy cases with right upper quadrant abdominal pain, six cases with a previous biliary-enteric anastomosis and clinical evidence of cholangitis, eight biliary strictures with pain or symptoms of cholangitis, four cases with strong clinical evidence of sclerosing cholangitis, three cases with suspected post-laparoscopic cholecystectomy bile leakage, and one case with chronic pancreatitis and a common bile duct stent associated with cholangitis. In relation to MRC, CTC provided additional biliary functional information as follows: abnormal biliary drainage through the ampulla in 7/9 cholecystectomy cases, impaired drainage in 3/6 biliary-enteric anastomoses, and complete obstruction in 2/8 biliary strictures. CTC diagnosed early sclerosing cholangitis in 4/4 cases and confirmed suspected bile leakage in 1/3 post-laparoscopic cholecystectomy patients, and the patency of the biliary stent in the patient with chronic pancreatitis. Thus, CTC provides clinically important information about the function and kinetics of bile and complements findings obtained by MRC.