Contrast-agent-based perfusion MRI code repository and testing framework: ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

PURPOSE: Software has a substantial impact on quantitative perfusion MRI values. The lack of generally accepted implementations, code sharing and transparent testing reduces reproducibility, hindering the use of perfusion MRI in clinical trials. To address these issues, the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI) aimed to establish a community-led, centralized repository for sharing open-source code for processing contrast-based perfusion imaging, incorporating an open-source testing framework. METHODS: A repository was established on the OSIPI GitHub website. Python was chosen as the target software language. Calls for code contributions were made to OSIPI members, the ISMRM Perfusion Study Group, and publicly via OSIPI websites. An automated unit-testing framework was implemented to evaluate the output of code contributions, including visual representation of the results. RESULTS: The repository hosts 86 implementations of perfusion processing steps contributed by 12 individuals or teams. These cover all core aspects of DCE- and DSC-MRI processing, including multiple implementations of the same functionality. Tests were developed for 52 implementations, covering five analysis steps. For T1 mapping, signal-to-concentration conversion and population AIF functions, different implementations resulted in near-identical output values. For the five pharmacokinetic models tested (Tofts, extended Tofts-Kety, Patlak, two-compartment exchange, and two-compartment uptake), differences in output parameters were observed between contributions. CONCLUSIONS: The OSIPI DCE-DSC code repository represents a novel community-led model for code sharing and testing. The repository facilitates the re-use of existing code and the benchmarking of new code, promoting enhanced reproducibility in quantitative perfusion imaging.

A community-endorsed open-source lexicon for contrast agent-based perfusion MRI: A consensus guidelines report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

This manuscript describes the ISMRM OSIPI (Open Science Initiative for Perfusion Imaging) lexicon for dynamic contrast-enhanced and dynamic susceptibility-contrast MRI. The lexicon was developed by Taskforce 4.2 of OSIPI to provide standardized definitions of commonly used quantities, models, and analysis processes with the aim of reducing reporting variability. The taskforce was established in February 2020 and consists of medical physicists, engineers, clinicians, data and computer scientists, and DICOM (Digital Imaging and Communications in Medicine) standard experts. Members of the taskforce collaborated via a slack channel and quarterly virtual meetings. Members participated by defining lexicon items and reporting formats that were reviewed by at least two other members of the taskforce. Version 1.0.0 of the lexicon was subject to open review from the wider perfusion imaging community between January and March 2022, and endorsed by the Perfusion Study Group of the ISMRM in the summer of 2022. The initial scope of the lexicon was set by the taskforce and defined such that it contained a basic set of quantities, processes, and models to enable users to report an end-to-end analysis pipeline including kinetic model fitting. We also provide guidance on how to easily incorporate lexicon items and definitions into free-text descriptions (e.g., in manuscripts and other documentation) and introduce an XML-based pipeline encoding format to encode analyses using lexicon definitions in standardized and extensible machine-readable code. The lexicon is designed to be open-source and extendable, enabling ongoing expansion of its content. We hope that widespread adoption of lexicon terminology and reporting formats described herein will increase reproducibility within the field.

Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects.

OBJECTIVE: Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. MATERIALS AND METHODS: BOLD images were acquired at 3 T in 14 healthy volunteers. [Formula: see text]-imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based [Formula: see text]-time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation. RESULTS: Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. DISCUSSION: Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.

Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI.

Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.

A Reperfusion BOLD-MRI Tissue Perfusion Protocol Reliably Differentiate Patients with Peripheral Arterial Occlusive Disease from Healthy Controls.

There is no established technique that directly quantifies lower limb tissue perfusion. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is an MRI technique that can determine skeletal muscle perfusion. BOLD-MRI relies on magnetic differences of oxygenated and deoxygenated hemoglobin, and regional changes in oxy/deoxyhemoglobin ratio can be recorded by T2* weighted MRI sequences. We aimed to test whether BOLD-MRI can differentiate lower limb tissue perfusion in peripheral arterial occlusive disease (PAOD) patients and healthy controls. Twenty-two PAOD patients and ten healthy elderly volunteers underwent lower limb BOLD-MRI. Reactive hyperemia was provoked by transient cuff compression and images of the gastrocnemius and soleus muscles were continuously acquired at rest, during ischemia and reperfusion. Key BOLD parameters were baseline T2* absolute value and time to T2* peak value after cuff deflation (TTP). Correlations between imaging parameters and ankle-brachial index (ABI) was investigated. The mean TTP was considerably prolonged in PAOD patients compared to healthy controls (m. gastrocnemius: 111 ± 46 versus 48 ± 22 s, p = 0.000253; m. soleus: 100 ± 42 versus 41 ± 30 s, p = 0.000216). Both gastrocnemius and soleus TTP values correlated strongly with ABI (-0.82 and -0.78, p < 0.01). BOLD-MRI during reactive hyperemia differentiated most PAOD patients from healthy controls. TTP was the most decisive parameter and strongly correlated with the ABI.

MRI diffusion and perfusion alterations in the mesencephalon and pons as markers of disease and symptom reversibility in idiopathic normal pressure hydrocephalus.

INTRODUCTION: Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. METHODS: Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3-6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. RESULTS: There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (rs = 0.80, p = 0.031 and rs = 0.66, p = 0.021, respectively). CONCLUSION: The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH.

Data-driven identification of tumor subregions based on intravoxel incoherent motion reveals association with proliferative activity.

PURPOSE: Intravoxel incoherent motion (IVIM) analysis gives information on tissue diffusion and perfusion and may thus have a potential for e.g. tumor tissue characterization. This work aims to study if clustering based on IVIM parameter maps can identify tumor subregions, and to assess the relevance of obtained subregions by histological analysis. METHODS: Fourteen mice with human neuroendocrine tumors were examined with diffusion-weighted imaging to obtain IVIM parameter maps. Gaussian mixture models with IVIM maps from all tumors as input were used to partition voxels into k clusters, where k = 2 was chosen for further analysis based on goodness of fit. Clustering was performed with and without the perfusion-related IVIM parameter D* , and with and without including spatial information. The validity of the clustering was assessed by comparison with corresponding histologically stained tumor sections. A Ki-67-based index quantifying the degree of tumor proliferation was considered appropriate for the comparison based on the obtained cluster characteristics. RESULTS: The clustering resulted in one class with low diffusion and high perfusion and another with slightly higher diffusion and low perfusion. Strong agreement was found between tumor subregions identified by clustering and subregions identified by histological analysis, both regarding size and spatial agreement. Neither D* nor spatial information had substantial effects on the clustering results. CONCLUSIONS: The results of this study show that IVIM parameter maps can be used to identify tumor subregions using a data-driven framework based on Gaussian mixture models. In the studied tumor model, the obtained subregions showed agreement with proliferative activity.

Pre-and postoperative cerebral blood flow changes in patients with idiopathic normal pressure hydrocephalus measured by computed tomography (CT)-perfusion.

In idiopathic normal pressure hydrocephalus (iNPH), the cerebral blood flow (CBF) is of pathophysiological interest and a potential biomarker. Computed tomography perfusion (CTP), an established technique with high spatial resolution and quantitative measurements, has not yet been used in the iNPH context. If CTP were sensitive to the CBF levels and changes in iNPH, this technique might provide diagnostic and prognostic absolute perfusion thresholds. The aim of this work was to determine the applicability of CTP to iNPH. CBF measurements of 18 patients pre- and 17 three months postoperatively, and six healthy individuals (HI) were evaluated in 12 cortical and subcortical regions of interest. Correlations between CBF and symptomatology were analyzed in shunt-responders. Compared to HI, the preoperative CBF in iNPH was significantly reduced in normal appearing and periventricular white matter (PVWM), the lentiform nucleus and the global parenchyma. No CBF differences were shown between responders and non-responders. In responders, the CBF recovered postoperatively by 2.5-32% to approximately the level of HI, but remained significantly decreased in the PVWM of non-responders. The pre- and postoperative CBF of cortical and subcortical regions correlated with the intensity of symptoms. In spite of limited spatial coverage, CTP can measure CBF changes in iNPH.

IMAGE FUSION OF RECONSTRUCTED DIGITAL TOMOSYNTHESIS VOLUMES FROM A FRONTAL AND A LATERAL ACQUISITION.

Digital tomosynthesis (DTS) has been used in chest imaging as a low radiation dose alternative to computed tomography (CT). Traditional DTS shows limitations in the spatial resolution in the out-of-plane dimension. As a first indication of whether a dual-plane dual-view (DPDV) DTS data acquisition can yield a fair resolution in all three spatial dimensions, a manual registration between a frontal and a lateral image volume was performed. An anthropomorphic chest phantom was scanned frontally and laterally using a linear DTS acquisition, at 120 kVp. The reconstructed image volumes were resampled and manually co-registered. Expert radiologist delineations of the mediastinal soft tissues enabled calculation of similarity metrics in regard to delineations in a reference CT volume. The fused volume produced the highest total overlap, implying that the fused volume was a more isotropic 3D representation of the examined object than the traditional chest DTS volumes.

In Patients With Idiopathic Normal Pressure Hydrocephalus Postoperative Cerebral Perfusion Changes Measured by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Correlate With Clinical Improvement.

OBJECTIVE: To explore relationships between clinical improvement and relative cerebral blood flow (rCBF) changes after shunt-insertion in idiopathic normal pressure hydrocephalus (iNPH) as measured by dynamic susceptibility contrast magnetic resonance imaging. METHODS: In 20 idiopathic normal pressure hydrocephalus patients rCBF was measured preoperatively and 3 months postoperatively. Because of shunt-induced right-sided artefacts, evaluation was restricted to 12 left-sided cortical, subcortical, and periventricular regions of interest. Correlations between rCBF and clinical symptoms were analyzed in shunt responders. RESULTS: In responders, the postoperative regions of interest-based rCBF increase of 2% to 9% was significant in the parenchyma, the hippocampus, and the anterior periventricular white matter. Perfusion improvement in the cingulus, caudate head, and thalamus correlated with decreased disturbance in one or more of the domains neuropsychology, gait, balance, and total performance. CONCLUSIONS: Apparently, dynamic susceptibility contrast magnetic resonance imaging can measure postoperative perfusion changes in responders. Postoperatively, perfusion increase in some grey matter structures seems to determine the degree of clinical improvement.