Ola Friman

CellProfiler: image analysis software for identifying and quantifying cell phenotypes

Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens and functional genomics (for example, using RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler. CellProfiler can address a variety of biological questions quantitatively, including standard assays (for example, cell count, size, per-cell protein levels) and complex morphological assays (for example, cell/organelle shape or subcellular patterns of DNA or protein staining).

Adaptive analysis of fMRI data

This article introduces novel and fundamental improvements of fMRI data analysis. Central is a technique termed constrained canonical correlation analysis, which can be viewed as a natural extension and generalization of the popular general linear model method. The concept of spatial basis filters is presented and shown to be a very successful way of adaptively filtering the fMRI data. A general method for designing suitable hemodynamic response models is also proposed and incorporated into the constrained canonical correlation approach. Results that demonstrate how each of these parts significantly improves the detection of brain activity, with a computation time well within limits for practical use, are provided.

Multiple hypothesis template tracking of small 3D vessel structures

A multiple hypothesis tracking approach to the segmentation of small 3D vessel structures is presented. By simultaneously tracking multiple hypothetical vessel trajectories, low contrast passages can be traversed, leading to an improved tracking performance in areas of low contrast. This work also contributes a novel mathematical vessel template model, with which an accurate vessel centerline extraction is obtained. The tracking is fast enough for interactive segmentation and can be combined with other segmentation techniques to form robust hybrid methods. This is demonstrated by segmenting both the liver arteries in CT angiography data, which is known to pose great challenges, and the coronary arteries in 32 CT cardiac angiography data sets in the Rotterdam Coronary Artery Algorithm Evaluation Framework, for which ground-truth centerlines are available.

Exploratory fMRI Analysis by Autocorrelation Maximization

A novel and computationally efficient method for exploratory analysis of functional MRI data is presented. The basic idea is to reveal underlying components in the fMRI data that have maximum autocorrelation. The tool for accomplishing this task is Canonical Correlation Analysis. The relation to Principal Component Analysis and Independent Component Analysis is discussed and the performance of the methods is compared using both simulated and real data.

Benchmarking framework for myocardial tracking and deformation algorithms: An open access database

In this paper we present a benchmarking framework for the validation of cardiac motion analysis algorithms. The reported methods are the response to an open challenge that was issued to the medical imaging community through a MICCAI workshop. The database included magnetic resonance (MR) and 3D ultrasound (3DUS) datasets from a dynamic phantom and 15 healthy volunteers. Participants processed 3D tagged MR datasets (3DTAG), cine steady state free precession MR datasets (SSFP) and 3DUS datasets, amounting to 1158 image volumes. Ground-truth for motion tracking was based on 12 landmarks (4 walls at 3 ventricular levels). They were manually tracked by two observers in the 3DTAG data over the whole cardiac cycle, using an in-house application with 4D visualization capabilities. The median of the inter-observer variability was computed for the phantom dataset (0.77 mm) and for the volunteer datasets (0.84 mm). The ground-truth was registered to 3DUS coordinates using a point based similarity transform. Four institutions responded to the challenge by providing motion estimates for the data: Fraunhofer MEVIS (MEVIS), Bremen, Germany; Imperial College London - University College London (IUCL), UK; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Inria-Asclepios project (INRIA), France. Details on the implementation and evaluation of the four methodologies are presented in this manuscript. The manually tracked landmarks were used to evaluate tracking accuracy of all methodologies. For 3DTAG, median values were computed over all time frames for the phantom dataset (MEVIS=1.20mm, IUCL=0.73 mm, UPF=1.10mm, INRIA=1.09 mm) and for the volunteer datasets (MEVIS=1.33 mm, IUCL=1.52 mm, UPF=1.09 mm, INRIA=1.32 mm). For 3DUS, median values were computed at end diastole and end systole for the phantom dataset (MEVIS=4.40 mm, UPF=3.48 mm, INRIA=4.78 mm) and for the volunteer datasets (MEVIS=3.51 mm, UPF=3.71 mm, INRIA=4.07 mm). For SSFP, median values were computed at end diastole and end systole for the phantom dataset(UPF=6.18 mm, INRIA=3.93 mm) and for the volunteer datasets (UPF=3.09 mm, INRIA=4.78 mm). Finally, strain curves were generated and qualitatively compared. Good agreement was found between the different modalities and methodologies, except for radial strain that showed a high variability in cases of lower image quality.

A Comprehensive Approach to the Analysis of Contrast Enhanced Cardiac MR Images

Current magnetic resonance imaging (MRI) technology allows the determination of patient-individual coronary tree structure, detection of infarctions, and assessment of myocardial perfusion. Joint inspection of these three aspects yields valuable information for therapy planning, e.g., through classification of myocardium into healthy tissue, regions showing a reversible hypoperfusion, and infarction with additional information on the corresponding supplying artery. Standard imaging protocols normally provide image data with different orientations, resolutions and coverages for each of the three aspects, which makes a direct comparison of analysis results difficult. The purpose of this work is to develop methods for the alignment and combined analysis of these images. The proposed approach is applied to 21 datasets of healthy and diseased patients from the clinical routine. The evaluation shows that, despite limitations due to typical MRI artifacts, combined inspection is feasible and can yield clinically useful information.

Detection and detrending in fMRI data analysis.

This article addresses the impact that colored noise, temporal filtering, and temporal detrending have on the fMRI analysis situation. Specifically, it is shown why the detection of event-related designs benefit more from pre-whitening than blocked designs in a colored noise structure. Both theoretical and empirical results are provided. Furthermore, a novel exploratory method for producing drift models that efficiently capture trends and drifts in the fMRI data is introduced. A comparison to currently employed detrending approaches is presented. It is shown that the novel exploratory model is able to remove a major part of the slowly varying drifts that are abundant in fMRI data. The value of such a model lies in its ability to remove drift components that otherwise would have contributed to a colored noise structure in the voxel time series.

Resampling fMRI time series

The problem of selecting a threshold for the statistical parameter maps in functional MRI (fMRI) is a delicate issue. The use of advanced test statistics and/or the complex dependence structure of fMRI noise may preclude parametric statistical methods for finding appropriate thresholds. Non-parametric statistical methodology has been presented as a feasible alternative. In this paper, we discuss resampling methods for finding thresholds in single subject fMRI analysis. It is shown that the presence of a BOLD response in the time series biases the estimation of the temporal autocorrelation, which in turn leads to biased thresholds. Therefore, proposed resampling methods based on Fourier and wavelet transforms, which employ implicit and weak models of the temporal noise characteristic, may produce erroneous thresholds. In contrast, resampling based on a pre-whitening transform, which is driven by an explicit noise model, is robust to the presence of a BOLD response. The size of the bias is, however, largely dependent on the complexity of the experimental design. While blocked designs can induce large biases, event-related designs generate significantly smaller biases. Results supporting these claims are provided.

Uncertainty in white matter fiber tractography

In this work we address the uncertainty associated with fiber paths obtained in white matter fiber tractography. This uncertainty, which arises for example from noise and partial volume effects, is quantified using a Bayesian modeling framework. The theory for estimating the probability of a connection between two areas in the brain is presented, and a new model of the local water diffusion profile is introduced. We also provide a theorem that facilitates the estimation of the parameters in this diffusion model, making the presented method simple to implement.

Detection of Neural Activity in fMRI Using Maximum Correlation Modeling

A technique for detecting neural activity in functional MRI data is introduced. It is based on a novel framework termed maximum correlation modeling. The method employs a spatial filtering approach that adapts to the local activity patterns, which results in an improved detection sensitivity combined with good specificity. A spatially varying hemodynamic response is simultaneously modelled by a sum of two gamma functions. Comparisons to traditional analysis methods are made using both synthetic and real data. The results indicate that the maximum correlation modeling approach is a strong alternative for analyzing fMRI data.