Dosimetric feasibility of direct post-operative MR-Linac-based stereotactic radiosurgery for resection cavities of brain metastases.

BACKGROUND: Post-operative radiosurgery (SRS) of brain metastases patients is typically planned on a post-recovery MRI, 2-4 weeks after resection. However, the intracranial metastasis may (re-)grow in this period. Planning SRS directly on the post-operative MRI enables shortening this time interval, anticipating the start of adjuvant systemic therapy, and so decreasing the chance of extracranial progression. The MRI-Linac (MRL) allows the simultaneous execution of the post-operative MRI and SRS treatment. The aim of this work was investigating the dosimetric feasibility of MRL-based post-operative SRS. METHODS: MRL treatments based on the direct post-operative MRI were simulated, including thirteen patients with resectable single brain metastases. The gross tumor volume (GTV) was contoured on the direct post-operative scans and compared to the post-recovery MRI GTV. Three plans for each patient were created: a non-coplanar VMAT CT-Linac plan (ncVMAT) and a coplanar IMRT MRL plan (cIMRT) on the direct post-operative MRI, and a ncVMAT plan on the post-recovery MRI as the current clinical standard. RESULTS: Between the direct post-operative and post-recovery MRI, 15.5 % of the cavities shrunk by > 2 cc, and 46 % expanded by ≥ 2 cc. Although the direct post-operative cIMRT plans had a higher median gradient index (3.6 vs 2.7) and median V3Gy of the skin (18.4 vs 1.1 cc) compared to ncVMAT plans, they were clinically acceptable. CONCLUSION: Direct post-operative MRL-based SRS for resection cavities of brain metastases is dosimetrically acceptable, with the advantages of increased patient comfort and logistics. Clinical benefit of this workflow should be investigated given the dosimetric plausibility.

Sensory processing sensitivity and axonal microarchitecture: identifying brain structural characteristics for behavior.

Previous research using functional MRI identified brain regions associated with sensory processing sensitivity (SPS), a proposed normal phenotype trait. To further validate SPS, to characterize it anatomically, and to test the usefulness in psychology of methodologies that assess axonal properties, the present study correlated SPS proxy questionnaire scores (adjusted for neuroticism) with diffusion tensor imaging (DTI) measures. Participants (n = 408) from the Human Connectome Project were studied. Voxelwise analysis showed that mean- and radial diffusivity correlated positively with SPS scores in the right and left subcallosal and anterior-ventral cingulum bundle, and the right forceps minor of the corpus callosum, all frontal cortex areas generally underlying emotion, motivation, and cognition. Further analyses showed correlations throughout medial frontal cortical regions in the right and left ventromedial prefrontal cortex, including the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate, and arcuate fasciculus. Fractional anisotropy was negatively correlated with SPS scores in white matter (WM) of the right premotor/motor/somatosensory/supramarginal gyrus regions. Region of interest (ROI) analysis showed small effect sizes (- 0.165 to 0.148) in WM of the precuneus and inferior frontal gyrus. Other ROI effects were found in the dorsal-, ventral visual pathways and primary auditory cortex. The results reveal that in a large group of participants, axonal microarchitectural differences can be identified with SPS traits that are subtle and in the range of typical behavior. The results suggest that the heightened sensory processing in people who show that SPS may be influenced by the microstructure of WM in specific cortical regions. Although previous fMRI studies had identified most of these areas, the DTI results put a new focus on brain areas related to attention and cognitive flexibility, empathy, emotion, and first levels of sensory processing, as in primary auditory cortex. Psychological trait characterization may benefit from DTI methodology by identifying influential brain systems for traits.

Quantifying the post-radiation accelerated brain aging rate in glioma patients with deep learning.

BACKGROUND AND PURPOSE: Changes of healthy appearing brain tissue after radiotherapy (RT) have been previously observed. Patients undergoing RT may have a higher risk of cognitive decline, leading to a reduced quality of life. The experienced tissue atrophy is similar to the effects of normal aging in healthy individuals. We propose a new way to quantify tissue changes after cranial RT as accelerated brain aging using the BrainAGE framework. MATERIALS AND METHODS: BrainAGE was applied to longitudinal MRI scans of 32 glioma patients. Utilizing a pre-trained deep learning model, brain age is estimated for all patients' pre-radiotherapy planning and follow-up MRI scans to acquire a quantification of the changes occurring in the brain over time. Saliency maps were extracted from the model to spatially identify which areas of the brain the deep learning model weighs highest for predicting age. The predicted ages from the deep learning model were used in a linear mixed effects model to quantify aging of patients after RT. RESULTS: The linear mixed effects model resulted in an accelerated aging rate of 2.78 years/year, a significant increase over a normal aging rate of 1 (p < 0.05, confidence interval = 2.54-3.02). Furthermore, the saliency maps showed numerous anatomically well-defined areas, e.g.: Heschl's gyrus among others, determined by the model as important for brain age prediction. CONCLUSION: We found that patients undergoing RT are affected by significant post-radiation accelerated aging, with several anatomically well-defined areas contributing to this aging. The estimated brain age could provide a method for quantifying quality of life post-radiotherapy.

Irradiation of the subventricular zone and subgranular zone in high- and low-grade glioma patients: an atlas-based analysis on overall survival.

BACKGROUND: Neural stem cells in the subventricular zone (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. METHODS: We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBrA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. RESULTS: Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, P < .001; multivariate: 1.103/Gy, P = .002) and SGZ dose (univariate: 1.023/Gy, P < .001; multivariate: 1.055/Gy, P < .001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high-/low-dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, P = .011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, P < .001). No correlations between dose and OS were found for LGG patients. CONCLUSION: Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

Diffusion kurtosis imaging of white matter in bipolar disorder.

White matter pathology likely contributes to the pathogenesis of bipolar disorder (BD). Most studies of white matter in BD have used diffusion tensor imaging (DTI), but the advent of more advanced multi-shell diffusion MRI imaging offers the possibility to investigate other aspects of white matter microstructure. Diffusion kurtosis imaging (DKI) extends the DTI model and provides additional measures related to diffusion restriction. Here, we investigated white matter in BD by applying whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution tractography to assess differences in DKI and DTI metrics between BD (n = 25) and controls (n = 24). The VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in DTI metrics following FDR-correction. The DKI findings indicate altered connectivity across cortical, subcortical and cerebellar areas in BD. DKI is sensitive to different microstructural properties and is a useful complementary technique to DTI to more fully investigate white matter in BD.

Dose-dependent volume loss in subcortical deep grey matter structures after cranial radiotherapy.

BACKGROUND AND PURPOSE: The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms. MATERIALS AND METHODS: We selected 31 patients treated with RT for grade II-IV glioma. Pre-RT and 1 year post-RT 3D T1-weighted MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age. RESULTS: A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16 to 1.37%/Gy, corresponding to 4.9-41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years. CONCLUSION: Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with higher volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.

Effect of radiation therapy on cerebral cortical thickness in glioma patients: Treatment-induced thinning of the healthy cortex.

BACKGROUND: With overall survival of brain tumors improving, radiation induced brain injury is becoming an increasing issue. One of the effects of radiation therapy (RT) is thinning of the cerebral cortex, which could be one of the factors contributing to cognitive impairments after treatment. In healthy brain, cortex thickness varies between 1 and 4.5 mm. In this study, we assess the effect of RT on the thickness of the cerebral cortex and relate the changes to the local dose. METHODS: We identified 28 glioma patients with optimal scan quality. Clinical CTs and MRIs at baseline and 1 year post-RT were collected and coregistered. The scans were processed via an automated image processing pipeline, which enabled measuring changes of the cortical thickness, which were related to local dose. RESULTS: Three areas were identified where significant dose-dependent thinning occurred, with thinning rates of 5, 6, and 26 µm/Gy after 1 year, which corresponds to losses of 5.4%, 7.2%, and 21.6% per 30 Gy per year. The first area was largely located in the right inferior parietal, supramarginal, and superior parietal regions, the second in the right posterior cingulate and paracentral regions, and the third almost completely in the right lateral orbital frontal region. CONCLUSIONS: We have identified three areas susceptible to dose-dependent cortical thinning after radiation therapy. Should future prospective studies conclude that irradiation of these areas lead to cognitive decline, they need to be spared in order to prevent this debilitating consequence of treatment.

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rTMS in major depressive disorder

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal. Methods: We investigated whether structural connectivity ­ derived from diffusion MRI data ­ could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS. Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS. Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients. Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted. Clinical trial registration: http://clinicaltrials.gov/show/NCT01832805

Regions of white matter abnormalities in the arcuate fasciculus in veterans with anger and aggression problems.

Aggression after military deployment is a common occurrence in veterans. Neurobiological research has shown that aggression is associated with a dysfunction in a network connecting brain regions implicated in threat processing and emotion regulation. However, aggression may also be related to deficits in networks underlying communication and social cognition. The uncinate and arcuate fasciculi are integral to these networks, thus studying potential abnormalities in these white matter connections can further our understanding of anger and aggression problems in military veterans. Here, we use diffusion tensor imaging tractography to investigate white matter microstructural properties of the uncinate fasciculus and the arcuate fasciculus in veterans with and without anger and aggression problems. A control tract, the parahippocampal cingulum was also included in the analyses. More specifically, fractional anisotropy (FA) estimates are derived along the trajectory from all fiber pathways and compared between both groups. No between-group FA differences are observed for the uncinate fasciculus and the cingulum, however parts of the arcuate fasciculus show a significantly lower FA in the group of veterans with aggression and anger problems. Our data suggest that abnormalities in arcuate fasciculus white matter connectivity that are related to self-regulation may play an important role in the etiology of anger and aggression in military veterans.

The adverse effect of gradient nonlinearities on diffusion MRI: From voxels to group studies.

Nonlinearities of gradient magnetic fields in diffusion MRI (dMRI) can introduce systematic errors in estimates of diffusion measures. While there are correction methods that can compensate for these errors, as presented in the Human Connectome Project, such nonlinear effects are often assumed to be negligible for typical applications, and as a result, gradient nonlinearities are mostly left uncorrected. In this work, we perform a systematic analysis to investigate the effect of gradient nonlinearities on dMRI studies, from voxel-wise estimates to group study outcomes. We present a novel framework to quantify and visualize these effects by decomposing them into their magnitude and angle components. Mean magnitude deviation and fractional gradient anisotropy are introduced to quantify the distortions in the size and shape of gradient vector distributions. By means of Monte-Carlo simulations and real data from the Human Connectome Project, the errors on dMRI measures derived from the diffusion tensor imaging and diffusional kurtosis imaging are highlighted. We perform a group study to showcase the alteration in the significance and effect size due to ignoring gradient nonlinearity correction. Our results indicate that the effect of gradient field nonlinearities on dMRI studies can be significant and may complicate the interpretation of the results and conclusions.

Author Correction: The challenge of mapping the human connectome based on diffusion tractography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Changes in cortical thickness and volume after cranial radiation treatment: A systematic review.

Cognitive decline has a clear impact on quality of life in patients who have received cranial radiation treatment. The pathophysiological process is most likely multifactorial, with a possible role for decreased cortical thickness and volume. As radiotherapy treatment systems are becoming more sophisticated, precise sparing of vulnerable regions and tissue is possible. This allows radiation oncologists to make treatment more patient-tailored. A systematic search was performed to collect and review all available evidence regarding the effect of cranial radiation treatment on cortical thickness and volume. We searched the Pubmed, Embase and Cochrane databases, with an additional reference check in the Scopus database. Studies that examined cortical changes on MRI within patients as well as between treated and non-treated patients were included. The quality of the studies was assessed with a checklist specially designed for this review. No meta-analysis was performed due to the lack of randomised trials. Out of 1915 publications twenty-one papers were selected, of which fifteen observed cortical changes after radiation therapy. Two papers reported radiation-dependent decrease in cortical thickness within patients one year after radiation treatment, suggesting a clear relation between the two. However, study quality was considered mostly suboptimal, and there was great inhomogeneity between the included studies. This means that, although there has been increasing interest in the effects of radiation treatment on cortex morphology, no reliable conclusion can be drawn based on the currently available evidence. This calls for more research, preferably with a sufficiently large patient population, and adequate methodology.

The Superoanterior Fasciculus (SAF): A Novel White Matter Pathway in the Human Brain?

Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain's circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that-to the best of our knowledge-has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe.

The challenge of mapping the human connectome based on diffusion tractography.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

Central sensitization-related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model.

Central sensitization is a key mechanism in the pathology of several neuropathic pain disorders. We aimed to investigate the underlying brain connectivity changes in a rat model of chronic pain. Non-noxious whisker stimulation was used to evoke blood-oxygen-level-dependent (BOLD) responses in a block-design functional Magnetic Resonance Imaging (fMRI) experiment on 9.4T. Measurements were repeated two days and one week after injecting complete Freund's adjuvant into the rats' whisker pad. We found that acute pain reduced activation in the barrel cortex, most probably due to a plateau effect. After one week, increased activation of the anterior cingulate cortex was found. Analyses of effective connectivity driven by stimulus-related activation revealed that chronic pain-related central sensitization manifested as a widespread alteration in the activity of the somatosensory network. Changes were mainly mediated by the anterior cingulate cortex and the striatum and affected the somatosensory and motor cortices and the superior colliculus. Functional connectivity analysis of nested BOLD oscillations justified that the anterior cingular-somatosensory interplay is a key element of network changes. Additionally, a decreased cingulo-motor functional connectivity implies that alterations also involve the output tract of the network. Our results extend the knowledge about the role of the cingulate cortex in the chronification of pain and indicate that integration of multiple connectivity analysis could be fruitful in studying the central sensitization in the pain matrix.

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials.

Ghrelin modulates the fMRI BOLD response of homeostatic and hedonic brain centers regulating energy balance in the rat.

The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the BOLD response to ghrelin.

Vascular action as the primary mechanism of cognitive effects of cholinergic, CNS-acting drugs, a rat phMRI BOLD study.

Concordant results of functional magnetic resonance imaging (fMRI) and behavioral tests prove that some non-blood-brain barrier-penetrating drugs produce robust central nervous system (CNS) effects. The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC. Donepezil-a highly CNS-penetrating cholinesterase inhibitor-prevents the negative BOLD and cognitive deficits regardless whether the provoking agent is scopolamine or butylscopolamine. Interestingly, the non-BBB-penetrating cholinesterase inhibitor neostigmine also prevents or substantially inhibits those cognitive and fMRI changes. Intact cerebral blood flow and optimal metabolism are crucial for the normal functioning of neurons and other cells in the brain. Drugs that are not BBB penetrating yet act on the CNS highlight the importance of unimpaired circulation, and point to the cerebral vasculature as a primary target for drug action in diseases where impaired circulation and consequently suboptimal energy metabolism are followed by upstream pathologic events.

Investigating the need of triggering the acquisition for infant diffusion MRI: a quantitative study including bootstrap statistics.

Diffusion weighted magnetic resonance imaging is increasingly being used for neonatal and young pediatric subjects. Our purpose was to investigate a) whether cardiac triggering was needed to reduce variability of diffusion (tensor) imaging data, b) how pulsation artifacts affect the fitted diffusion tensor when triggering is not used and c) the feasibility of triggered data acquisition in neonates and young children. Data were collected from 11 infants and 7 adults. In seven infants and seven adults, diffusion encoding was applied solely along the z gradient direction with and without cardiac triggering. Non-parametric bootstrap statistical methods were applied to investigate the dependence of variance on triggering. One infant and all adults served as test-retest controls. From the remaining three infants diffusion tensor imaging data were acquired with and without triggering. Our findings that used the repeated measurements in a single diffusion-encoding direction indicated that without triggering the variability in the data was increased significantly both in infants and adults. When collecting diffusion tensor data in infants, this increased variability results in erroneous fractional anisotropy values and artifactual fiber direction estimates. Contrary to previous reports but supported by our findings involving adults, pulsation artifacts were present in a larger extent of the brain in the infant population. In conclusion, triggering is feasible in young subjects and is preferred when acquiring diffusion MRI data. In doing so, the amount of erroneous estimations due to image artifacts will be minimized, which in turn will lead to more specific and less ambiguous interpretations. Although fitting the pulse-monitoring device requires additional set-up time, the total imaging time is usually shorter than acquiring multiple data sets to compile a single, artifact-free set.