Evaluation of image quality, radiation dose and diagnostic performance of dual-energy CT datasets in patients with hepatocellular carcinoma.

AIM: To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. MATERIAL AND METHODS: Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. RESULTS: Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets (p>0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p=0.001; mixed versus 140 kVp, p=0.001; 80 kVp versus mixed, p=0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets (p<0.001). CONCLUSIONS: The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel imaging-guided surgical technique that allows the performance of noninvasive and radiation-free ablation. Presently, computed tomography (CT)-guided radiofrequency ablation, a minimally invasive percutaneous technique, is the standard for treating symptomatic osteoid osteomas. The purpose of this study was to evaluate the use of MRgFUS ablation for the treatment of nonspinal osteoid osteomas in terms of technical success, complications, and clinical success through one year of follow-up. METHODS: In this prospective multicenter study, thirty consecutive patients with a nonspinal osteoid osteoma were enrolled between May 2010 and April 2012 at three different university centers; twenty-nine of the patients were treated with use of MRgFUS. Lesions had been previously diagnosed on the basis of imaging, including dynamic contrast-enhanced MR. The mean number of sonications and energy deposition were determined. Technical success was evaluated through an assessment of complications immediately after treatment. Clinical success was determined on the basis of pain reduction as measured with a visual analog scale (VAS), recurrence, and long-term complications through twelve months. RESULTS: Technical success of MRgFUS was observed for all twenty-nine patients. The mean number of sonications (and standard deviation) was 7 ± 3, and the mean delivered acoustic energy was 1180 ± 736 J. At the twelve-month follow-up, complete clinical success was observed in twenty-six (90%) of the twenty-nine patients (95% confidence interval [CI] = 84 to 95; mean VAS, 0 ± 0 points). Partial success was observed in three (10%) of the twenty-nine patients (95% CI = 5 to 16; mean VAS score, 5 ± 0 points); two of these patients subsequently underwent CT-guided radiofrequency ablation, and one underwent open surgery. Pain score values showed a significant reduction (p < 0.001) between baseline (mean VAS score, 8 ± 1 points) and post treatment (mean VAS score, 1 ± 2 points). No complications were observed. CONCLUSIONS: MRgFUS may be an effective and safe alternative approach in the treatment of nonspinal osteoid osteoma. A complete clinical success rate of 90% was demonstrated without adverse events. MRgFUS is totally noninvasive and eliminates radiation exposure.

Guard cell anion channel SLAC1 is regulated by CDPK protein kinases with distinct Ca2+ affinities.

In response to drought stress, the phytohormone abscisic acid (ABA) induces stomatal closure. Thereby the stress hormone activates guard cell anion channels in a calcium-dependent, as well as -independent, manner. Open stomata 1 protein kinase (OST1) and ABI1 protein phosphatase (ABA insensitive 1) represent key components of calcium-independent ABA signaling. Recently, the guard cell anion channel SLAC1 was identified. When expressed heterologously SLAC1 remained electrically silent. Upon coexpression with Ca(2+)-independent OST1, however, SLAC1 anion channels appear activated in an ABI1-dependent manner. Mutants lacking distinct calcium-dependent protein kinases (CPKs) appeared impaired in ABA stimulation of guard cell ion channels, too. To study SLAC1 activation via the calcium-dependent ABA pathway, we studied the SLAC1 response to CPKs in the Xenopus laevis oocyte system. Split YFP-based protein-protein interaction assays, using SLAC1 as the bait, identified guard cell expressed CPK21 and 23 as major interacting partners. Upon coexpression of SLAC1 with CPK21 and 23, anion currents document SLAC1 stimulation by these guard cell protein kinases. Ca(2+)-sensitive activation of SLAC1, however, could be assigned to the CPK21 pathway only because CPK23 turned out to be rather Ca(2+)-insensitive. In line with activation by OST1, CPK activation of the guard cell anion channel was suppressed by ABI1. Thus the CPK and OST1 branch of ABA signal transduction in guard cells seem to converge on the level of SLAC1 under the control of the ABI1/ABA-receptor complex.

Preliminary experience with MRA in evaluating the degree of carotid stenosis and plaque morphology using high-resolution sequences after gadofosveset trisodium (Vasovist) administration: comparison with CTA and DSA.

PURPOSE: The authors performed a preliminary study with blood-pool contrast-enhanced magnetic resonance angiography (MRA) in evaluating the degree of carotid artery stenosis and plaque morphology, comparing the diagnostic performance of first-pass (FP) and steady-state (SS) acquisitions with 64-slice computed tomography angiography (CTA) and using digital subtraction angiography (DSA) as the reference standard. MATERIALS AND METHODS: Twenty patients with >or=50% carotid artery stenosis at Doppler sonography underwent blood-pool contrast-enhanced MRA, CTA and DSA. Two independent radiologists evaluated MRA and CTA examinations to assess the degree of stenosis and characterise plaque morphology. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for FP, SS and CTA. The McNemar and Wilcoxon tests were used to determine significant differences (p<0.05) between the diagnostic performance of the three modalities. RESULTS: Forty carotid bifurcations were studied. For stenosis grading, accuracy, sensitivity, specificity, PPV and NPV were 90%, 89%, 90%, 89% and 90%, respectively, at FP; 95%, 95%, 95%, 95% and 95%, respectively, at SS; and 97.5%, 95%, 100%, 100% and 95%, respectively, at CTA. SS and CTA were superior to FP for evaluating the degree of stenosis (p<0.05). For evaluating plaque morphology, accuracy, sensitivity, specificity, PPV and NPV were 87.5%, 89%, 86%, 85% and 90%, respectively, at FP; 97.5%, 100%, 95%, 95% and 100%, respectively, at SS; and 100%, 100%, 100%, 100% and 100%, respectively, at CTA. There were no significant differences between FP, SS and CTA for plaque assessment (p>0.05). CONCLUSIONS: Blood-pool contrast-enhanced MRA with SS sequences allow improved diagnostic evaluation of the degree of carotid stenosis and plaque morphology compared with FP and is substantially equal to CTA and DSA.

TEM, HRTEM, electron holography and electron tomography studies of gamma' and gamma'' nanoparticles in Inconel 718 superalloy.

The aim of the study was the identification of gamma' and gamma'' strengthening precipitates in a commercial nickel-base superalloy Inconel 718 (Ni-19Fe-18Cr-5Nb-3Mo-1Ti-0.5Al-0.04C, wt %) using TEM dark-field, HRTEM, electron holography and electron tomography imaging. To identify gamma' and gamma'' nanoparticles unambiguously, a systematic analysis of experimental and theoretical diffraction patterns were performed. Using HRTEM method it was possible to analyse small areas of precipitates appearance. Electron holography and electron tomography techniques show new possibilities of visualization of gamma' and gamma'' nanoparticles. The analysis by means of different complementary TEM methods showed that gamma'' particles exhibit a shape of thin plates, while gamma' phase precipitates are almost spherical.

Diagnostic performance of 64-MDCT and 1.5-T MRI with high-resolution sequences in the T staging of gastric cancer: a comparative analysis with histopathology.

PURPOSE: This study was undertaken to compare the accuracy of magnetic resonance (MR) imaging and 64-slice multidetector computed tomography (64-MDCT) in the T staging of gastric carcinoma in comparison with histopathology. MATERIALS AND METHODS: Forty patients with an endoscopic diagnosis of gastric carcinoma underwent preoperative MR imaging and 64-MDCT, both of which were performed after i.v. injection of scopolamine and water distension of the stomach. In the MR imaging protocol, we acquired T2-weighted turbo spin-echo (TSE) sequences, true fast imaging steady-state free precession (true-FISP) and gadolinium-enhanced T1-weighted volumetric interpolated breath-hold examination (VIBE) 3D sequences. Contrastenhanced CT scans were obtained in the arterial and venous phases. Two groups of radiologists independently reviewed the MR and 64-MDCT images. The results were compared with pathology findings. RESULTS: In the evaluation of T stage, 64-MDCT had 82.5% and MR imaging had 80% sensitivity. Accuracy of MR imaging was slightly higher than that of 64-MDCT in identifying T1 lesions (50% vs 37.5%), whereas the accuracy of 64-MDCT was higher in differentiating T2 lesions (81.2% vs 68.7%). The accuracy of MR imaging and 64-MDCT did not differ significantly in the evaluation of T3-T4 lesions (p>0.05). Understaging was observed in 20% of cases with MR imaging and in 17.5% with 64-MDCT. CONCLUSIONS: MR imaging and 64-MDCT accuracy levels did not differ in advanced stages of disease, whereas MR imaging was superior in identifying early stages of gastric cancer and can be considered a valid alternative to MDCT in clinical practice.

Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.

Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.

Encephalomyelopathy and polyneuropathy associated with neuronal vacuolation in two Boxer littermates.

Neuronal vacuolation and spinocerebellar degeneration is a rare, presumably inherited condition that is reported only in Rottweilers and in crossbred dogs with known or potential Rottweiler heritage. Gross and histopathologic findings include laryngeal muscle atrophy, neuronal vacuolation, and a combined central and peripheral axonopathy. Two 6-month-old Boxer puppies from the same litter were referred for evaluation of progressive pelvic limb paresis and ataxia, upper airway stridor, and visual deficits. Examination of each dog suggested a combined myelopathy and peripheral neuropathy, as well as congenital ocular disease. Gross lesions were limited to atrophy of the intrinsic laryngeal muscles. Histopathologically, there was diffuse loss of axons and myelin in the dorsolateral and ventral funiculi throughout the spinal cord and extending into the caudal aspect of the brain stem. Vacuolation of scattered neuronal cell bodies was present in the spinal cord and selected brain stem nuclei. Multifocal axonal degeneration and demyelination was observed in the recurrent laryngeal nerve, sciatic nerve, and brachial plexus and was most severe in the recurrent laryngeal nerve. Ocular abnormalities included microphthalmia, cataracts, and retinal dysplasia. The findings in these Boxer dogs, unrelated to the Rottweiler breed, are analogous to the syndrome of neuronal vacuolation and spinocerebellar degeneration reported in Rottweilers.

Optimisation of a high-resolution whole-body MR angiography protocol with parallel imaging and biphasic administration of a single bolus of Gd-BOPTA: preliminary experience in the systemic evaluation of atherosclerotic burden in patients referred for endovascular procedures.

PURPOSE: This study was performed to validate a high-resolution whole-body magnetic resonance angiography (MRA) protocol with parallel imaging and biphasic administration of a single bolus of contrast agent in the preliminary assessment of systemic atherosclerotic burden in patients referred for endovascular procedures. MATERIALS AND METHODS: Forty patients referred for endovascular treatment of atherosclerotic disease of the carotid arteries (n=23), peripheral vessels (n=14) or aorta (n=3) on the basis of previous clinical and diagnostic examinations underwent high-resolution whole-body MRA at 1.5 T with 3D spoiled gradient recalled echo (GRE) sequences, featuring parallel imaging acquisition technique with x2 acceleration factor. Sixty-eight surface coil elements and a four-station imaging protocol were employed. Biphasic intravenous administration of a paramagnetic contrast agent [gadolinium benzyloxyproprionic-tetraacetic acid (Gd-BOPTA)] was performed with the following protocol: 10 ml at a speed of 1 ml/s followed by further 10 ml at a speed of 0.5 ml/s. For image analysis, the arterial system was divided into 42 segments for evaluation. The presence or absence of atherosclerotic lesions was evaluated by two observers in consensus; segments were classified as having clinically significant disease (>or=50% stenosis or an aneurysmal dilatation) or no significant disease (<50% stenosis). The presence of stenoocclusive disease, determined at all segments, was compared with findings on digital subtraction angiography (DSA), which were interpreted by a third independent reader. Sensitivity, specificity and concordance of whole-body MRA findings with DSA were calculated, and receiver operating characteristic (ROC) analysis was performed for all vascular territories. RESULTS: A total of 1,680 arterial segments was evaluated; 138 (8.3%) were affected by atherosclerotic alterations. Carotid lesions were confirmed in 23 patients (34 segments), involvement of peripheral vessels in 14 (57 segments) and abdominal aneurysms in three. Sensitivity and specificity of whole-body MRA were, respectively, 95%-97% for head and neck vessels, 100%-100% for thoracoabdominal vessels, 98%-97% for thigh vessels and 84%-88% for calf vessels; concordance with the DSA findings was significant (p<0.05). Subclinical atherosclerotic lesions were evidenced in 25 patients, involving carotid arteries (12 segments), peripheral vessels (21 segments) and abdominal aorta (one segment). All these lesions were confirmed by a second modality, and ten of these patients required further care. CONCLUSIONS: High-resolution whole-body MRA with Gd-BOPTA may be considered a reliable modality for imaging systemic atherosclerosis in candidates for endovascular procedures. The subclinical detection of the total atherosclerotic burden has potential implications for secondary care in this population.

64-MDCT imaging of the coronary arteries and systemic arterial vascular tree in a single examination: optimisation of the scan protocol and contrast-agent administration.

PURPOSE: The aim of this study was to validate a 64-row multidetector computed tomography (64-MDCT) acquisition protocol with biphasic administration of contrast medium for comprehensive assessment of the coronary and systemic arterial tree in a single examination. MATERIALS AND METHODS: The scanning protocol comprised two acquisitions: an electrocardiograph (ECG)-gated scan at the level of the heart, followed by a total-body, low-dose scan of the systemic arterial circulation. Twenty patients were evaluated using two different strategies for contrast administration. In ten patients, the delay between the two acquisitions was set at 40 s, whereas in the remaining patients, it varied between 45 s and 65 s. For both strategies, the degree of systemic arterial opacification and the attenuation gradient between arterial and venous structures were quantitatively assessed at six extracoronary locations. Two observers evaluated in consensus the presence or absence of atherosclerosis and the degree of stenosis of arterial segments. RESULTS: Three hundred coronary segments were analysed. Arterial-wall changes were depicted in 155 (51%) segments, and in 35 (23%), the degree of stenosis was > 50%. Of the 640 extracoronary arterial segments, 250 (39%) presented atherosclerotic wall alterations, in 50 (20%), the degree of stenosis was > 50% and five were affected by aneurysmal dilatation. The magnitude of arterial opacification values and attenuation gradients between arterial and venous structures were significantly higher in patients scanned with the 40-s fixed-delay strategy. CONCLUSIONS: Whole-body CT angiography with biphasic administration of contrast agent and fixed scan delay has been shown to be a feasible and reproducible technique. Comprehensive data on the global atherosclerotic burden potentially offer important therapeutic options for subclinical, high-risk segments.

Diagnosing mycobacterial lymphadenitis in children using fine needle aspiration biopsy: cytomorphology, ZN staining and autofluorescence -- making more of less.

Although the incidence of TB has stabilized or declined in most world regions, it is increasing in Africa, Southeast Asia, and the Eastern Mediterranean, fuelled by the HIV pandemic. More than 4,000 people died daily from TB-related illnesses in 2005. TB is a major cause of childhood morbidity and mortality in these developing countries, and there is an urgent need for rapid and definitive modalities for mycobacterial diagnosis in children. This prospective study in Tygerberg Hospital, Cape Town, South Africa, evaluates the ability of fine needle aspiration biopsy (FNAB) to diagnose mycobacterial lymphadenitis in children, using cytomorphology, autofluorescence on Papanicolaou stained smears, Ziehl-Nielsen (ZN) staining and/or culture. FNABs were performed on 200 children, and 25 (12.5%) aspirates were inadequate. Cultures were positive in 79/175 (45%); Mycobacterium tuberculosis was identified in 61 and Mycobacterium bovis BCG in 18 cases. Using culture as the gold standard, the concordance of the different techniques was as follows: cytomorphology 70%, ZN staining 73%, and autofluorescence 68%. Using an alternative gold standard (culture positive and/or suggestive cytomorphology plus positive autofluorescence or ZN smear), the "true" diagnostic performance of the various techniques was as follows: cytomorphology-sensitivity 78%, specificity 91%, positive predictive value (PPV) 93%, ZN staining - sensitivity 62%%, specificity 97%, PPV 97%; autofluorescence-sensitivity 67%, specificity 97%, PPV 97%; and culture-sensitivity 75%, specificity 100%, and PPV 100%. FNAB was shown to provide a rapid and definitive diagnosis in the majority of cases of suspected tuberculous lymphadenitis in children, based on cytomorphology and identification of the organism.

[Successful individualized and targeted therapy of an NSCLC patient with Gefitinib based on a predictive assessment of the EGF-receptor mutation status]. / Erfolgreiche individualisierte zielgerichtete Gefitinib-Therapie beim NSCLC nach prädiktiver Mutationsanalyse des EGF Rezeptors.

BACKGROUND: Molecular alterations in the tyrosine kinase (TK) domain of the human epidermal growth factor receptor (EGFR) have been correlated with tumour remission upon treatment with the TK inhibitor Gefitinib in non-small cell lung cancer (NSCLC). We have retrospectively investigated the correlation of point mutations with clinical response and, based on our retrospective results, used predictive molecular assessment as the basis for treatment in one patient. METHODS: Mutational analysis was performed in 11 NSCLC-patients (10 responders, 1 non-responder) among 62 patients treated with Gefitinib within an expanded access program. RESULTS: Activating molecular alterations were found in 8/11 investigated samples (point mutations in exons 18 and 21, deletions in exon 19). All molecular changes were found in adenocarcinoma or bronchioloalveolar carcinoma. The tumours of two male responders with squamous cell carcinoma showed either a wild-type sequence or carried a nonsense mutation. In one patient treatment with Gefitinib after prospective assessment of mutations resulted in tumour remission and thus proved to be predictive. CONCLUSIONS: Mutations in the EGFR TK domain correlate with the clinical response to Gefitinib. The predictive assessment of molecular alterations may thus be helpful for treatment decisions in selected cases. A clinical response to Gefitinib is nevertheless also found in patients with wild-type EGFR.

Online system for faster multipoint linkage analysis via parallel execution on thousands of personal computers.

Computation of LOD scores is a valuable tool for mapping disease-susceptibility genes in the study of Mendelian and complex diseases. However, computation of exact multipoint likelihoods of large inbred pedigrees with extensive missing data is often beyond the capabilities of a single computer. We present a distributed system called "SUPERLINK-ONLINE," for the computation of multipoint LOD scores of large inbred pedigrees. It achieves high performance via the efficient parallelization of the algorithms in SUPERLINK, a state-of-the-art serial program for these tasks, and through the use of the idle cycles of thousands of personal computers. The main algorithmic challenge has been to efficiently split a large task for distributed execution in a highly dynamic, nondedicated running environment. Notably, the system is available online, which allows computationally intensive analyses to be performed with no need for either the installation of software or the maintenance of a complicated distributed environment. As the system was being developed, it was extensively tested by collaborating medical centers worldwide on a variety of real data sets, some of which are presented in this article.

Investigation of the possible association between nosocomial candiduria and candidaemia.

This study aimed to determine whether candiduria is associated with the occurrence of nosocomial candidaemia. In the case-control part of the study, 115 cases (nosocomial candidaemia) and 115 controls (nosocomial bacteraemia) were similar in age, severity of condition and time of hospitalisation. There was a significant association of candidaemia with candiduria (OR 9.79; 95% CI 2.14-44.76). In the microbiology part of the study, 23 pairs of Candida-positive urine and blood cultures were obtained from 23 patients. In ten (43%) cases, the urine and blood culture isolates belonged to different species, and molecular typing showed a difference in two of the 13 cases yielding the same species from both specimens. Overall, there was a significant association between candiduria and candidaemia, but the Candida isolates from urine and blood were different for 52% of the patients. Thus, the data indicated that the urinary tract was probably not a source for the candidaemia.

Modeling haplotype block variation using Markov chains.

Models of background variation in genomic regions form the basis of linkage disequilibrium mapping methods. In this work we analyze a background model that groups SNPs into haplotype blocks and represents the dependencies between blocks by a Markov chain. We develop an error measure to compare the performance of this model against the common model that assumes that blocks are independent. By examining data from the International Haplotype Mapping project, we show how the Markov model over haplotype blocks is most accurate when representing blocks in strong linkage disequilibrium. This contrasts with the independent model, which is rendered less accurate by linkage disequilibrium. We provide a theoretical explanation for this surprising property of the Markov model and relate its behavior to allele diversity.

[Non-small-cell lung cancer third-line therapy with gefitinib]. / Drittlinientherapie mit Gefitinib beim nicht-kleinzelligen Bronchialkarzinom.

The EGFR-inhibition via tyrosine-kinase-inhibitor gefitinib (Iressa) constitutes a new way to treat non-small-cell lung cancer. Recent research results enable us to better understand the basics of molecular targeted therapy (MTT). These results are helpful to re-interpret the clinical results obtained so far for gefitinib and to consider for the first time in a predictive manner factors for the selection of patients suitable for therapy. Three case reports are presented in this paper which illustrate that -- with view to the results from translational research -- the use of gefitinib offers an efficient new therapeutic modality for the treatment of chemotherapy-resistant non-small-cell lung cancer.

AtTPK4, an Arabidopsis tandem-pore K+ channel, poised to control the pollen membrane voltage in a pH- and Ca2+-dependent manner.

The Arabidopsis tandem-pore K(+) (TPK) channels displaying four transmembrane domains and two pore regions share structural homologies with their animal counterparts of the KCNK family. In contrast to the Shaker-like Arabidopsis channels (six transmembrane domains/one pore region), the functional properties and the biological role of plant TPK channels have not been elucidated yet. Here, we show that AtTPK4 (KCO4) localizes to the plasma membrane and is predominantly expressed in pollen. AtTPK4 (KCO4) resembles the electrical properties of a voltage-independent K(+) channel after expression in Xenopus oocytes and yeast. Hyperpolarizing as well as depolarizing membrane voltages elicited instantaneous K(+) currents, which were blocked by extracellular calcium and cytoplasmic protons. Functional complementation assays using a K(+) transport-deficient yeast confirmed the biophysical and pharmacological properties of the AtTPK4 channel. The features of AtTPK4 point toward a role in potassium homeostasis and membrane voltage control of the growing pollen tube. Thus, AtTPK4 represents a member of plant tandem-pore-K(+) channels, resembling the characteristics of its animal counterparts as well as plant-specific features with respect to modulation of channel activity by acidosis and calcium.

High density linkage disequilibrium mapping using models of haplotype block variation.

MOTIVATION: The presence of millions of single nucleotide polymorphisms (SNPs) in the human genome has spurred interest in genetic mapping methods based on linkage disequilibrium. The recently discovered haplotype block structure of human variation promises to improve the effectiveness of these methods. A key difficulty for mapping techniques is the cost involved in separately identifying the haplotypes on each of an individual's chromosomes. RESULTS: We present a new approach for performing linkage disequilibrium mapping using high density haplotype or genotype data. Our method is based on a statistical model of haplotype block variation, which takes account of recombination hotspots, bottlenecks, genetic drift and mutation. We test our technique on two empirically determined high density datasets, attempting to recover the location of an SNP which was hidden and converted into phenotype information. We compare the results against a mapping method based on individual SNPs as well as a competing haplotype-based approach. We show that our strategy significantly outperforms these other approaches when used as a guide for resequencing and that it can also deal with both unphased genotype data and low penetrance diseases. AVAILABILITY: HaploBlock executables for Linux, Mac OS X and Sun OS, as well as user documentation, are available online at http://bioinfo.cs.technion.ac.il/haploblock/