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1.
Eur Radiol ; 28(10): 4111-4121, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29713770

ABSTRACT

OBJECTIVES: We aimed to assess the diagnostic performance of a combined protocol with coronary computed tomography angiography (CCTA) and stress CT perfusion imaging (CTP) in heart transplant patients for comprehensive morphological and functional imaging. METHODS: In this prospective study, 13 patients undergoing routine follow-up 8±6 years after heart transplantation underwent CCTA and dynamic adenosine stress CTP using a third-generation dual-source CT scanner, cardiac magnetic resonance (MR) adenosine stress perfusion imaging at 1.5 T, and catheter coronary angiography. In CCTA stenoses >50% luminal diameter narrowing were noted. Myocardial perfusion deficits were documented in CTP and MR. Quantitative myocardial blood flow (MBF) was calculated with CTP. Left ventricular ejection fraction was determined on cardiac MR cine images. Radiation doses of CT were determined. RESULTS: One of the 13 patients had to be excluded because of severe motion artifacts. CCTA identified three patients with stenosis >50%, which were confirmed with catheter coronary angiography. CTP showed four patients with stress-induced myocardial hypoperfusion, which were confirmed by MR stress perfusion imaging. Quantitative analysis of global MBF showed lower mean values as compared to known reference values (MBF under stress 125.5 ± 34.5 ml/100 ml/min). Average left ventricular ejection fraction was preserved (56 ± 5%). CONCLUSIONS: In heart transplant patients, a comprehensive CT protocol for the assessment of morphology and function including CCTA and CTP showed good concordance to results from MR perfusion imaging and catheter coronary angiography. KEY POINTS: • Stress CT perfusion imaging enables the detection of myocardial ischemia • CT myocardial perfusion imaging can be combined with coronary computed tomography angiography • Combining perfusion and coronary CT imaging is accurate in heart transplant patients • CT myocardial perfusion imaging can be performed at a reasonable radiation dose.


Subject(s)
Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Heart Transplantation , Myocardial Perfusion Imaging/methods , Adult , Aged , Coronary Stenosis/physiopathology , Female , Heart/physiopathology , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Prospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
2.
Eur Radiol ; 24(4): 834-40, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24258277

ABSTRACT

OBJECTIVES: To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. METHODS: Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as "conventional CT", and DE-CT interpretations were evaluated and compared with follow-up CT. RESULTS: Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. CONCLUSIONS: Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. KEY POINTS: • Contrast material and haemorrhage have similar density on conventional 120-kV CT. • Contrast material hinders interpretation of CT in stroke patients after recanalisation. • Iodine and haemorrhage have different attenuation at lower kVs. • Dual energy CT improves accuracy in early differentiation of haemorrhage and contrast extravasation. • Early differentiation between iodine and haemorrhage helps to initiate therapy promptly.


Subject(s)
Cerebral Hemorrhage/diagnostic imaging , Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging , Mechanical Thrombolysis/adverse effects , Stroke/therapy , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Algorithms , Brain/blood supply , Cerebral Hemorrhage/etiology , Contrast Media/analysis , Female , Humans , Iodine/analysis , Male , Middle Aged , Young Adult
3.
Eur Radiol ; 23(9): 2475-81, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23660773

ABSTRACT

OBJECTIVES: To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. METHODS: Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. RESULTS: Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CONCLUSION: CT perfusion of kidney allografts may help to differentiate between ATN and rejection. KEY POINTS: • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.


Subject(s)
Graft Rejection/diagnosis , Graft Rejection/physiopathology , Kidney Transplantation/methods , Kidney/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Angiography/methods , Blood Flow Velocity , Contrast Media/pharmacology , Female , Humans , Image Processing, Computer-Assisted , Kidney/blood supply , Kidney Tubular Necrosis, Acute/diagnosis , Kidney Tubular Necrosis, Acute/pathology , Male , Middle Aged , Necrosis , Perfusion , Retrospective Studies , Software , Ultrasonography, Doppler/methods
4.
Eur Radiol ; 22(7): 1430-41, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22367468

ABSTRACT

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.


Subject(s)
Contrast Media/standards , Forecasting , Neoplasms/diagnostic imaging , Neovascularization, Pathologic/diagnostic imaging , Practice Guidelines as Topic , Tomography, X-Ray Computed/standards , Tomography, X-Ray Computed/trends , Humans , Neoplasms/blood supply , Reference Standards
5.
J Exp Med ; 176(5): 1399-404, 1992 Nov 01.
Article in English | MEDLINE | ID: mdl-1402684

ABSTRACT

The rearrangement of immunoglobulin (Ig) and T cell receptor (TCR) genes requires the activity of an as yet undefined V(D)J recombinase. One component of the recombinase appears to be a terminal transferase which may be involved in the addition of untemplated nucleotides (N regions) to the V(D)J joints. It has been observed that rearranged Ig and TCR genes isolated from fetal liver have few if any N regions, whereas in the adult mouse, these genes have a large number of untemplated nucleotides. The presence of N regions greatly alters the composition of the third hypervariable, complementarity determining region of the respective proteins, thus playing a major role in the conformation of the binding site. It was possible that, for functional reasons, N region-containing Ig and TCR genes were not permissible at the fetal stage of development. We have produced transgenic mice with a rearrangement test gene which, after V-J recombination, does not result in the production of functional Ig or TCR proteins. We report here that the rearrangement products have no N regions in fetal liver, but that the majority of joints in adult lymphoid tissues have N additions. The study is also an interesting demonstration of the randomness of rearrangements and the enormous variability that can be created from a single pair of V and J sequences.


Subject(s)
Gene Rearrangement , Genes, Immunoglobulin , Immunoglobulin Joining Region/genetics , Immunoglobulin Variable Region/genetics , Lymphoid Tissue/immunology , Receptors, Antigen, T-Cell/genetics , Animals , Base Sequence , Fetus/immunology , Immunoglobulin Heavy Chains/genetics , Mice , Mice, Inbred Strains , Mice, Transgenic , Molecular Sequence Data , Repetitive Sequences, Nucleic Acid
6.
J Exp Med ; 188(4): 689-98, 1998 Aug 17.
Article in English | MEDLINE | ID: mdl-9705951

ABSTRACT

Immunoglobulin (Ig) genes expressed in mature B lymphocytes can undergo somatic hypermutation upon cell interaction with antigen and T cells. The mutation mechanism had previously been shown to depend upon transcription initiation, suggesting that a mutator factor was loaded on an RNA polymerase initiating at the promoter and causing mutations during elongation (Peters, A., and U. Storb. 1996. Immunity. 4:57-65). To further elucidate this process we have created an artificial substrate consisting of alternating EcoRV and PvuII restriction enzyme sites (EPS) located within the variable (V) region of an Ig transgene. This substrate can easily be assayed for the presence of mutations in DNA from transgenic lymphocytes by amplifying the EPS insert and determining by restriction enzyme digestion whether any of the restriction sites have been altered. Surprisingly, the EPS insert was mutated many times more frequently than the flanking Ig sequences. In addition there were striking differences in mutability of the different nucleotides within the restriction sites. The data favor a model of somatic hypermutation where the fine specificity of the mutations is determined by nucleotide sequence preferences of a mutator factor, and where the general site of mutagenesis is determined by the pausing of the RNA polymerase due to secondary structures within the nascent RNA.


Subject(s)
Immunoglobulin Variable Region/genetics , Immunoglobulin kappa-Chains/genetics , Mutagenesis, Insertional , RNA , Animals , Base Sequence , Binding Sites , DNA, Complementary , Deoxyribonucleases, Type II Site-Specific , Immunoglobulin Joining Region/genetics , Mice , Mice, Transgenic , Molecular Sequence Data , Nucleic Acid Conformation , RNA/chemistry , RNA/metabolism , Transgenes
7.
J Int Med Res ; 36(4): 748-59, 2008.
Article in English | MEDLINE | ID: mdl-18652771

ABSTRACT

We determined the effects of combinations of C1 esterase inhibitor (C1-INH) with factor XIII and of N-acetylcysteine (NAC) with tirilazad mesylate (TM) during lipo-polysaccharide (LPS)-induced endotoxaemia in rats. Forty Wistar rats were divided into four groups: the control (CON) group received no LPS; the LPS, C1-INH + factor XIII and NAC + TM groups received endotoxin infusions (5 mg/kg per h). After 30 min of endotoxaemia, 100 U/kg C1-INH + 50 U/kg factor XIII was administered to the C1-INH + factor XIII group, and 150 mg/kg NAC + 10 mg/kg TM was administered in the NAC + TM group. Administration of C1-INH + factor XIII and NAC + TM both resulted in reduced leucocyte adherence and reduced levels of interleukin-1beta (IL-1beta). The LPS-induced increase in IL-6 levels was amplified by both drug combinations. There was no significant effect on mesenteric plasma extravasation. In conclusion, the administration of C1-INH + factor XIII and NAC + TM reduced endothelial leucocyte adherence and IL-1beta plasma levels, but increased IL-6 levels.


Subject(s)
Acetylcysteine/therapeutic use , Complement C1 Inhibitor Protein/therapeutic use , Cytokines/blood , Endotoxemia , Factor XIII/therapeutic use , Leukocytes/metabolism , Pregnatrienes/therapeutic use , Animals , Antioxidants/therapeutic use , Cell Adhesion/physiology , Cytokines/immunology , Drug Therapy, Combination , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Endotoxemia/drug therapy , Endotoxemia/immunology , Humans , Leukocytes/cytology , Male , Random Allocation , Rats , Rats, Wistar
8.
Clin Hemorheol Microcirc ; 39(1-4): 99-111, 2008.
Article in English | MEDLINE | ID: mdl-18503116

ABSTRACT

INTRODUCTION: The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats. METHODS: In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1beta (IL-1beta), interferone gamma (IFN-gamma) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor alpha (TNF-alpha), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated. RESULTS: After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD.Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma plasma levels were not influenced by NAC or TM administration. CONCLUSIONS: In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model.


Subject(s)
Acetylcysteine/pharmacology , Capillaries/drug effects , Cytokines/metabolism , Endotoxemia/blood , Intestines/blood supply , Leukocytes/cytology , Pregnatrienes/pharmacology , Animals , Antioxidants/pharmacology , Capillaries/metabolism , Cell Adhesion , Endotoxins/metabolism , Heart Rate , Leukocytes/drug effects , Leukocytes/metabolism , Male , Rats , Rats, Wistar
9.
AJNR Am J Neuroradiol ; 28(7): 1362-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17698541

ABSTRACT

BACKGROUND AND PURPOSE: Bone-subtraction techniques have been shown to enhance CT angiography (CTA) interpretation, but motion can lead to incomplete bone removal. The aim of this study was to evaluate 2 novel registration techniques to compensate for patient motion. MATERIALS AND METHODS: Fifty-four patients underwent bone-subtraction CTA (BSCTA) for the evaluation of the neck vessels with 64-section CT. We tested 3 different registration procedures: pure rigid registration (BSCTA), slab-based registration (SB-BSCTA), and a partially rigid registration (PR-BSCTA) approach. Subtraction quality for the assessment of different vascular segments was evaluated by 2 examiners in a blinded fashion. The Cohen kappa test was applied for interobserver variability, and the Wilcoxon signed rank test, for differences between the procedures. Motion between the corresponding datasets was measured and plotted against image-quality scores. RESULTS: Algorithms with motion compensation revealed higher image-quality scores (SB-BSCTA, mean 4.31; PR-BSCTA, mean 4.43) than pure rigid registration (BSCTA, mean 3.88). PR-BSCTA was rated superior to SB-BSCTA for the evaluation of the cervical internal and external carotid arteries (P<.001), whereas there was no significant difference for the other vessels (P=.157-.655). Both algorithms were clearly superior to pure rigid registration for all vessels except the basilar and ophthalmic artery. Interobserver agreement was high (kappa=0.46-0.98). CONCLUSION: Bone-subtraction algorithms with motion compensation provided higher image-quality scores than pure rigid registration methods, especially in cases with complex motion. PR-BSCTA was rated superior to SB-BSCTA in the visualization of the internal and external carotid arteries.


Subject(s)
Artifacts , Bone and Bones/diagnostic imaging , Cerebral Angiography/methods , Image Enhancement/methods , Subtraction Technique , Tomography, X-Ray Computed/methods , Head/blood supply , Head/diagnostic imaging , Humans , Image Interpretation, Computer-Assisted/methods , Motion , Neck/blood supply , Neck/diagnostic imaging , Reproducibility of Results , Sensitivity and Specificity
10.
Med Trop (Mars) ; 67(6): 601-6, 2007 Dec.
Article in French | MEDLINE | ID: mdl-18300523

ABSTRACT

Management of type II diabetes in sub-Saharan Africa presents a number of aspects that must be analyzed successively. Regarding the continent of Africa, implementing a strategy to control diabetes will require extensive information and education campaigns not only for health care workers but also for the general population as well as the creation of adequate infrastructure to optimize the availability of treatment. Regarding care modalities in Africa, the overall principles of management are the same as anywhere in the world. However these modalities must be adapted to the sociocultural environment of the patient. Objectives must be simplified without compromising the scientific requirements. Regarding patients, African perceptions about the disease are very different from those taught in Western schools. The different ethnocultural components of the disease must be recognized in order to optimize overall patient management.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Adult , Africa South of the Sahara/epidemiology , Diabetes Complications/prevention & control , Female , Health Policy , Humans , Hypertension/epidemiology , Male , Patient Education as Topic , Primary Prevention
11.
Bone Rep ; 7: 83-89, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29018837

ABSTRACT

We investigated the association between bone mineral density (BMD) and breast cancer risk in a large prospective cohort and quantified the evidence in a meta-analysis of prospective studies. Baseline BMD has been measured by dual energy X-ray absorptiometry (DXA, N = 1418). Data on medication and lifestyle has been collected by questionnaire. Cox proportional Hazards models were applied to calculate Hazard Ratios for breast cancer. In addition, a meta-analysis on categorical and dose-response values including the current results has been performed applying random-effects models. During mean follow-up of 16.3 (SD 3.3) years of 1380 women (mean age 55.5 ± 6.3 years), 52 cases of invasive breast cancer were identified. We found no statistically significant association of BMD with breast cancer risk (per one z-score increase, HR 0.91, 95% CI 0.67-1.23). In the meta-analysis, however, breast cancer risk increased by 15% and 16% per 0.1 g/m2 increase in BMD at the lumbar spine (95% CI 0.99-1.33) and at the femoral neck (95% CI 1.02-1.32), respectively. Compared to the lowest, the HRs for breast cancer were statistically significant for the highest BMD category, i.e. 1.49 (95% CI 1.04-2.13) at the lumbar spine and 1.66 (95% CI 1.26-2.18) at the femur. We found no association between BMD (DXA) and breast cancer risk in our cohort. However, overall the present meta-analysis extends and confirms the statistically significant association between increasing BMD and increased breast cancer risk.

12.
AJNR Am J Neuroradiol ; 27(1): 55-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16418356

ABSTRACT

PURPOSE: CT angiography (CTA) has been established for detection and therapy planning of intracranial aneurysms. The analysis of aneurysms at the level of the skull base, however, remains difficult because bone prevents a free view. We report initial clinical results of an approach for automatic bone elimination from CTA data. MATERIAL AND METHODS: Before the bone-removal process 2 datasets are acquired: nonenhanced spiral CT with reduced dose and contrast-enhanced CTA. The software automatically registers the nonenhanced data onto the CTA data and selectively removes bone. Vascular structures, as well as brain tissue, remain visible. In this study, we investigated 27 patients with 29 aneurysms, 13 of which were located at the skull base. 3D volume-rendered images with and without bone removal were reviewed and compared with digital subtraction angiography by 2 radiologists in consensus. RESULTS: All supraclinoidal aneurysms were detected on 3D volume-rendered images of both CTA and bone-subtraction CT angiography (BSCTA). Four intracavernous and 3 paraclinoid aneurysms of the internal carotid artery were not visible or were only partially visible on conventional 3D CTA, whereas they could be optimally visualized with BSCTA. Bone removal was successful in all patients; the average additional time for postprocessing was 6.2 minutes. In 7 patients (26%), perfect bone removal without any artifacts was achieved. In most patients, some bone remnants were still present, though it did not disturb the 3D visualization of vascular structures. CONCLUSION: BSCTA allows robust and fast selective elimination of bony structures, thus ascertaining a better analysis of arteries at the level of the skull base. This is useful for both detection and therapy planning of intracranial aneurysms.


Subject(s)
Angiography, Digital Subtraction , Cerebral Angiography , Intracranial Aneurysm/diagnostic imaging , Tomography, X-Ray Computed , Carotid Artery, Internal/diagnostic imaging , Contrast Media , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Ophthalmic Artery/diagnostic imaging , Skull , Tomography, Spiral Computed
13.
Curr Top Microbiol Immunol ; 182: 137-41, 1992.
Article in English | MEDLINE | ID: mdl-1490348

ABSTRACT

Transgenic mice are discussed which carry a rearrangement test transgene. The methylation status of the transgene varies, depending on the background mouse strain. When the transgene is bred into the C57BL/6 strain, it is completely methylated and not rearranged in lymphoid organs. After several generations of crossing into DBA/2 or SJL the transgene becomes unmethylated and rearranges at high frequency. A strain specific modifier of DNA methylation (Ssm-1) was mapped close to the Friend virus susceptibility locus (Fv-1) on mouse chromosome 4. Rearranged transgenes from spleen, bone marrow and thymus of adult mice or fetal liver were cloned and sequenced. A great variety of joints was found, with about 1/3 being in the correct reading frame. Small deletions into the V- and J-coding ends as well as N region additions contributed to the variability. The fetal joints showed no N regions. Since no functional immunoglobulin (Ig) gene can be created from this artificial test gene, the data indicate that the rearrangement mechanism of the fetus differs from that of the adult.


Subject(s)
Genes, Immunoglobulin , Animals , DNA/chemistry , DNA/genetics , Female , Gene Expression , Gene Rearrangement , Male , Methylation , Mice , Mice, Transgenic , Pedigree
14.
Rofo ; 177(1): 17-23, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15657816

ABSTRACT

PURPOSE: The purpose of our preliminary animal study was to evaluate the feasibility of a new subtraction technique for visualization of perfusion defects within the lung parenchyma in segmental and subsegmental pulmonary embolism (PE). MATERIALS AND METHODS: In three healthy pigs, PE were artificially induced by fresh human clot material. Within a single breath-hold, CT angiography (CTA) was performed on a 16-slice multi-slice CT scanner (SOMATOM Sensation 16; Siemens, Forchheim, Germany) before and after intravenous application of 80 mL of contrast-medium, followed by a saline chaser. Scan parameters were 120 kV and 100 mAs (eff.), using a collimation of 16 x 1.5 mm and a table speed/rot. of 36 mm (pitch: 1.5; rotation time: 0.5 s). A new 3D subtraction technique was developed, which is based on automated segmentation, non-linear spatial filtering and non-rigid registration. Data were analysed using a color-encoded "compound view" of parenchymal enhancement and CTA information displayed in axial, coronal and sagittal orientation. RESULTS: Subtraction was technically feasible in all three data sets. The mean scan time for each series was 4.7 s, interscan delay was 14.7 s, respectively. Therefore, an average breath-hold of approximately 24 s was required for the overall scanning procedure. Downstream of occluded segmental and subsegmental arteries, perfusion defects were clearly assessable, showing lower or missing enhancement compared to normally perfused lung parenchyma. In all pigs, additional peripheral areas with triangular shaped perfusion defects were delineated, considered typical for PE. CONCLUSIONS: Our initial results from the animal model studied show that perfusion imaging of PE is feasible within a single breath-hold. It allows a comprehensive assessment of perfusion deficits as the direct proof of a pulmonary embolus, can be combined with an indirect visual quantification of the density changes in the adjacent lung tissue.


Subject(s)
Angiography , Pulmonary Embolism/diagnostic imaging , Subtraction Technique , Tomography, Spiral Computed , Tomography, X-Ray Computed/methods , Acute Disease , Animals , Disease Models, Animal , Feasibility Studies , Swine
15.
Int J Dev Biol ; 42(7): 977-82, 1998.
Article in English | MEDLINE | ID: mdl-9853828

ABSTRACT

This review describes studies on somatic hypermutation of immunoglobulin genes that were started in the mid-80s in collaboration with Ralph Brinster. Almost all of the experiments were carried out using Ig transgenes as targets for the somatic mutation mechanism. Ig transgenes can be very good targets of somatic mutation, despite many different transgene integration sites. Thus, the required cis-acting elements must be present within the approximately 10 kb of the transgene. Only the Ig variable region and its proximate flanks are mutated, not the constant region in unmanipulated sequences. Several Ig gene enhancers are permissive for somatic mutation and they do not have to be associated with the Ig promoter they normally interact with. However, the mutation process does seem to be specific for Ig genes. No mutations were found in several housekeeping genes isolated from cells that had very high levels of somatic hypermutation of their Ig genes. This suggests that the Ig enhancers provide the lg gene specificity. An exception is the Bcl-6 gene, encoding a transcription factor, which was found to be mutated in normal human memory B cells. When the transcriptional promoter that is located upstream of the variable region is duplicated upstream of the constant region, this region is mutated as well. This suggests a transcription coupled model in which a mutator factor associates with the RNA polymerase at the initiation of transcription, travels with the polymerase during elongation, and causes mutations during polymerase pausing. Our recent data with an artificial substrate for somatic mutation suggest that the mutations are increased by increased stability of the secondary structures in the nascent RNA, and the specific nucleotides that are mutated are due to preferences of a mutator factor.


Subject(s)
Genes, Immunoglobulin , Transgenes , Animals , Humans , Mice , Mice, Transgenic , Mutagenesis
16.
Phys Med Biol ; 60(21): 8567-82, 2015 Nov 07.
Article in English | MEDLINE | ID: mdl-26501360

ABSTRACT

In CT imaging, a variety of applications exist which are strongly SNR limited. However, in some cases redundant data of the same body region provide additional quanta. Examples in dual energy CT, the spatial resolution has to be compromised to provide good SNR for material decomposition. However, the respective spectral dataset of the same body region provides additional quanta which might be utilized to improve SNR of each spectral component. Perfusion CT is a high dose application, and dose reduction is highly desirable. However, a meaningful evaluation of perfusion parameters might be impaired by noisy time frames. On the other hand, the SNR of the average of all time frames is extremely high.In redundant CT acquisitions, multiple image datasets can be reconstructed and averaged to composite image data. These composite image data, however, might be compromised with respect to contrast resolution and/or spatial resolution and/or temporal resolution. These observations bring us to the idea of transferring high SNR of composite image data to low SNR 'source' image data, while maintaining their resolution.It has been shown that the noise characteristics of CT image data can be improved by iterative reconstruction (Popescu et al 2012 Book of Abstracts, 2nd CT Meeting (Salt Lake City, UT) p 148). In case of data dependent Gaussian noise it can be modelled with image-based iterative reconstruction at least in an approximate manner (Bruder et al 2011 Proc. SPIE 7961 79610J). We present a generalized update equation in image space, consisting of a linear combination of the previous update, a correction term which is constrained by the source image data, and a regularization prior, which is initialized by the composite image data. This iterative reconstruction approach we call bimodal reconstruction (BMR). Based on simulation data it is shown that BMR can improve low contrast detectability, substantially reduces the noise power and has the potential to recover spatial resolution of the source image data.For different CT applications: dual energy imaging, liver imaging, spiral imaging, cardiac imaging, we show that SNR can efficiently be transferred from the composite image to the source image data at constant patient dose, while maintaining resolution properties of the source data.


Subject(s)
Tomography, X-Ray Computed/methods , Algorithms , Radiation Dosage
17.
Stroke ; 32(2): 431-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11157178

ABSTRACT

BACKGROUND AND PURPOSE: Besides the delineation of hypoperfused brain tissue, the characterization of ischemia with respect to severity is of major clinical relevance, because the degree of hypoperfusion is the most critical factor in determining whether an ischemic lesion becomes an infarct or represents viable brain tissue. CT perfusion imaging yields a set of perfusion related parameters which might be useful to describe the hemodynamic status of the ischemic brain. Our objective was to determine whether measurements of the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative time to peak (rTP) can be used to differentiate areas undergoing infarction from reversible ischemic tissue. METHODS: In 34 patients with acute hemispheric ischemic stroke <6 hours after onset, perfusion CT was used to calculate rCBF, rCBV, and rTP values from areas of ischemic cortical and subcortical gray matter. Results were obtained separately from areas of infarction and noninfarction, according to the findings on follow-up imaging studies. The efficiency of each parameter to predict tissue outcome was tested. RESULTS: There was a significant difference between infarct and peri-infarct tissue for both rCBF and rCBV but not for rTP. Threshold values of 0.48 and 0.60 for rCBF and rCBV, respectively, were found to discriminate best between areas of infarction and noninfarction, with the efficiency of the rCBV being slightly superior to that of rCBF. The prediction of tissue outcome could not be increased by using a combination of various perfusion parameters. CONCLUSIONS: The assessment of cerebral ischemia by means of perfusion parameters derived from perfusion CT provides valuable information to predict tissue outcome. Quantitative analyses of the severity of ischemic lesions should be implemented into the diagnostic management of stroke patients.


Subject(s)
Brain Ischemia/diagnosis , Brain/blood supply , Brain/diagnostic imaging , Cerebrovascular Circulation , Tomography, X-Ray Computed/methods , Aged , Blood Flow Velocity , Blood Volume , Brain/pathology , Brain Ischemia/therapy , Catheterization , Contrast Media/pharmacokinetics , Discriminant Analysis , Female , Humans , Magnetic Resonance Imaging , Male , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Sensitivity and Specificity , Severity of Illness Index , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Treatment Outcome
18.
AJNR Am J Neuroradiol ; 21(8): 1441-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11003276

ABSTRACT

BACKGROUND AND PURPOSE: Because cerebral perfusion imaging for acute stroke is unavailable in most hospitals, we investigated the feasibility of a method of perfusion scanning that can be performed rapidly during standard cranial CT. Our aim was to identify the scanning parameters best suited to indicate tissue at risk and to measure a perfusion limit to predict infarction. METHODS: Seventy patients who had suffered stroke and had undergone cranial CT 0.5 to 12 hours (median, 3.75 hr) after the onset of symptoms participated in the study. While undergoing conventional CT, each patient received a bolus of iodinated contrast medium. Maps of time to peak (TTP), cerebral blood volume (CBV), and CBF were calculated from the resulting dynamically enhanced scans. These perfusion images were compared with follow-up CT scans or MR images showing the final infarctions. RESULTS: CBF maps predicted the extent of cerebral infarction with a sensitivity of 93% and a specificity of 98%. In contrast, CBV maps were less sensitive and TTP maps were less specific and also showed areas of collateral flow. Infarction occurred in all of the patients with CBF reduction of more than 70% and in half of the patients with CBF reduction of 40% to 70%. CONCLUSION: Dynamic CT perfusion imaging safely detects tissue at risk in cases of acute stroke and is a feasible method for any clinic with a third-generation CT scanner.


Subject(s)
Cerebrovascular Circulation , Stroke/diagnostic imaging , Stroke/physiopathology , Tomography, X-Ray Computed/methods , Acute Disease , Adult , Aged , Aged, 80 and over , Blood Volume , Brain Ischemia/diagnostic imaging , Brain Mapping , Cerebral Infarction/diagnostic imaging , Feasibility Studies , Female , Forecasting , Humans , Ischemic Attack, Transient/diagnostic imaging , Male , Microcirculation , Middle Aged , Risk Factors , Sensitivity and Specificity
19.
Med Phys ; 13(3): 334-9, 1986.
Article in English | MEDLINE | ID: mdl-3724693

ABSTRACT

We report the evaluation of a prototype dual-energy implementation using rapid kVp switching on a clinical computed tomographic scanner. The method employs prereconstruction basis material decomposition of the dual-energy projection data. Each dual-energy scan can be processed into conventional single-kVp images, basis material density images, and monoenergetic images. Phantom studies were carried out to qualitatively and quantitatively evaluate and validate the approach.


Subject(s)
Radiographic Image Enhancement/methods , Tomography, X-Ray Computed/methods , Biometry , Evaluation Studies as Topic , Health Physics , Humans , Models, Anatomic , Motion
20.
Med Phys ; 12(4): 431-6, 1985.
Article in English | MEDLINE | ID: mdl-4033587

ABSTRACT

A new nonlinear reconstruction method for tomosynthesis is described. This method is suited for "dilute" objects, i.e., objects in which most of the voxels have negligibly small absorption. Images of blood vessels filled with contrast material approximate this condition if the background is subtracted. The technique has been tested experimentally using a wire phantom and a prepared human heart. The results show significantly less artifacts than the well-known back projection. It is possible to get diagnostic image quality with a few projections. The reconstruction algorithm can be realized with dedicated real-time hardware.


Subject(s)
Angiography/methods , Tomography, X-Ray Computed/methods , Biophysical Phenomena , Biophysics , Heart/diagnostic imaging , Humans , Models, Structural
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