# Publications

## 2023

Paul E Neumann, Michael W Halle, Jian Kong, and Ron Kikinis. 2023. . Clin Anat.

Acupuncture point names written in Chinese Han characters often provide clinically useful information in both their literal and figurative meanings about location and therapeutic use. The World Health Organization (WHO) standard acupuncture nomenclature includes these names in Han characters in an unusual array that includes both "original" forms and, in parentheses, simplified forms. Construction of a multilingual table of acupuncture point names during development of a database revealed that the assumption that the "original" form in the WHO nomenclature was the traditional Chinese character was frequently false. The Han character forms in the pdf of the 2009 reprint of WHO Standard Acupuncture Point Locations were carefully compared with Han characters used in traditional and simplified Chinese, Japanese and Korean writing systems. This work utilized three online tools: UnicodePlus, Unihan Database Lookup, and Wiktionary. Only 48% of the "original" character forms were traditional Chinese characters. The Unicode number was correct in 99%, but in most cases the East Asian font used was not a traditional Chinese one. The issue about Han character forms was also found in all earlier versions of the WHO standard acupuncture nomenclature. Other detected problems included the use of wrong characters for an "original" character form in one name and for a simplified character form in another name. The WHO standard acupuncture nomenclature should be revised with a focus on accuracy in the usage of Han characters.

Arthur Chakwizira, Carl-Fredrik Westin, Jan Brabec, Samo Lasič, Linda Knutsson, Filip Szczepankiewicz, and Markus Nilsson. 2023. . NMR Biomed, 36, 1, Pp. e4827.
Monitoring time dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can lead to errors in parameter estimates. In this work, we propose a signal representation that incorporates the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, eliminating the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrization of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we found that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. The proposed signal representation was evaluated using Monte Carlo simulations in identical parallel cylinders with hexagonal and random packing as well as parallel cylinders with gamma-distributed radii. Results showed that the approach is sensitive to sizes in the interval 4-12 μm $$\upmu \mathrmm$$ and exchange rates in the simulated range of 0 to 20 s - 1 $$\mathrms^-1$$ , but also that there is a sensitivity to the extracellular geometry. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as a guide to protocol design capable of separating the two effects.
Hanneke M Keijzer, Marco Duering, Ofer Pasternak, Frederick J A Meijer, Marlous M L H Verhulst, Bart A R Tonino, Michiel J Blans, Cornelia W E Hoedemaekers, Catharina J M Klijn, and Jeannette Hofmeijer. 2023. . Eur Radiol, 33, 3, Pp. 2139-48.
OBJECTIVES: Approximately 50% of comatose patients after cardiac arrest never regain consciousness. Cerebral ischaemia may lead to cytotoxic and/or vasogenic oedema, which can be detected by diffusion tensor imaging (DTI). Here, we evaluate the potential value of free water corrected mean diffusivity (MD) and fractional anisotropy (FA) based on DTI, for the prediction of neurological recovery of comatose patients after cardiac arrest. METHODS: A total of 50 patients after cardiac arrest were included in this prospective cohort study in two Dutch hospitals. DTI was obtained 2-4 days after cardiac arrest. Outcome was assessed at 6 months, dichotomised as poor (cerebral performance category 3-5; n = 20) or good (n = 30) neurological outcome. We calculated the whole brain mean MD and FA and compared between patients with good and poor outcomes. In addition, we compared a preliminary prediction model based on clinical parameters with or without the addition of MD and FA. RESULTS: We found significant differences between patients with good and poor outcome of mean MD (good: 726 [702-740] × 10-6 mm2/s vs. poor: 663 [575-736] × 10-6 mm2/s; p = 0.01) and mean FA (0.30 ± 0.03 vs. 0.28 ± 0.03; p = 0.03). An exploratory prediction model combining clinical parameters, MD and FA increased the sensitivity for reliable prediction of poor outcome from 60 to 85%, compared to the model containing clinical parameters only, but confidence intervals are overlapping. CONCLUSIONS: Free water-corrected MD and FA discriminate between patients with good and poor outcomes after cardiac arrest and hold the potential to add to multimodal outcome prediction. KEY POINTS: • Whole brain mean MD and FA differ between patients with good and poor outcome after cardiac arrest. • Free water-corrected MD can better discriminate between patients with good and poor outcome than uncorrected MD. • A combination of free water-corrected MD (sensitive to grey matter abnormalities) and FA (sensitive to white matter abnormalities) holds potential to add to the prediction of outcome.

## 2022

Borjan Gagoski, Junshen Xu, Paul Wighton, M, Robert Frost, Wei-Ching Lo, Polina Golland, Andre van der Kouwe, Elfar Adalsteinsson, and P. 2022. . Magn Reson Med, 87, 4, Pp. 1914-22.

PURPOSE: Fetal brain Magnetic Resonance Imaging suffers from unpredictable and unconstrained fetal motion that causes severe image artifacts even with half-Fourier single-shot fast spin echo (HASTE) readouts. This work presents the implementation of a closed-loop pipeline that automatically detects and reacquires HASTE images that were degraded by fetal motion without any human interaction. METHODS: A convolutional neural network that performs automatic image quality assessment (IQA) was run on an external GPU-equipped computer that was connected to the internal network of the MRI scanner. The modified HASTE pulse sequence sent each image to the external computer, where the IQA convolutional neural network evaluated it, and then the IQA score was sent back to the sequence. At the end of the HASTE stack, the IQA scores from all the slices were sorted, and only slices with the lowest scores (corresponding to the slices with worst image quality) were reacquired. RESULTS: The closed-loop HASTE acquisition framework was tested on 10 pregnant mothers, for a total of 73 acquisitions of our modified HASTE sequence. The IQA convolutional neural network, which was successfully employed by our modified sequence in real time, achieved an accuracy of 85.2% and area under the receiver operator characteristic of 0.899. CONCLUSION: The proposed acquisition/reconstruction pipeline was shown to successfully identify and automatically reacquire only the motion degraded fetal brain HASTE slices in the prescribed stack. This minimizes the overall time spent on HASTE acquisitions by avoiding the need to repeat the entire stack if only few slices in the stack are motion-degraded.

Leo R Zekelman, Fan Zhang, Nikos Makris, Jianzhong He, Yuqian Chen, Tengfei Xue, Daniela Liera, Daniel L Drane, Yogesh Rathi, Alexandra J Golby, and Lauren J O Donnell. 2022. . Neuroimage, 246, Pp. 118739.

Language and theory of mind (ToM) are the cognitive capacities that allow for the successful interpretation and expression of meaning. While functional MRI investigations are able to consistently localize language and ToM to specific cortical regions, diffusion MRI investigations point to an inconsistent and sometimes overlapping set of white matter tracts associated with these two cognitive domains. To further examine the white matter tracts that may underlie these domains, we use a two-tensor tractography method to investigate the white matter microstructure of 809 participants from the Human Connectome Project. 20 association white matter tracts (10 in each hemisphere) are uniquely identified by leveraging a neuroanatomist-curated automated white matter tract atlas. The mean fractional anisotropy (FA), mean diffusivity (MD), and number of streamlines (NoS) are measured for each white matter tract. Performance on neuropsychological assessments of semantic memory (NIH Toolbox Picture Vocabulary Test, TPVT) and emotion perception (Penn Emotion Recognition Test, PERT) are used to measure critical subcomponents of the language and ToM networks, respectively. Regression models are constructed to examine how structural measurements of left and right white matter tracts influence performance across these two assessments. We find that semantic memory performance is influenced by the number of streamlines of the left superior longitudinal fasciculus III (SLF-III), and emotion perception performance is influenced by the number of streamlines of the right SLF-III. Additionally, we find that performance on both semantic memory & emotion perception is influenced by the FA of the left arcuate fasciculus (AF). The results point to multiple, overlapping white matter tracts that underlie the cognitive domains of language and ToM. Results are discussed in terms of hemispheric dominance and concordance with prior investigations.

David J Robles, Ammar Dharani, Kenneth A Rostowsky, Nikhil N Chaudhari, Van Ngo, Fan Zhang, Lauren J O Donnell, Lauren Green, Nasim Sheikh-Bahaei, Helena C Chui, and Andrei Irimia. 2022. . Geroscience, 44, 1, Pp. 83-102.

Little is known on how mild traumatic brain injury affects white matter based on age at injury, sex, cerebral microbleeds, and time since injury. Here, we study the fractional anisotropy of white matter to study these effects in 109 participants aged 18-77 (46 females, age μ ± σ = 40 ± 17 years) imaged within [Formula: see text] 1 week and [Formula: see text] 6 months post-injury. Age is found to be linearly associated with white matter degradation, likely due not only to injury but also to cumulative effects of other pathologies and to their interactions with injury. Age is associated with mean anisotropy decreases in the corpus callosum, middle longitudinal fasciculi, inferior longitudinal and occipitofrontal fasciculi, and superficial frontal and temporal fasciculi. Over [Formula: see text] 6 months, the mean anisotropies of the corpus callosum, left superficial frontal fasciculi, and left corticospinal tract decrease significantly. Independently of other predictors, age and cerebral microbleeds contribute to anisotropy decrease in the callosal genu. Chronically, the white matter of commissural tracts, left superficial frontal fasciculi, and left corticospinal tract degrade appreciably, independently of other predictors. Our findings suggest that large commissural and intra-hemispheric structures are at high risk for post-traumatic degradation. This study identifies detailed neuroanatomic substrates consistent with brain injury patients’ age-dependent deficits in information processing speed, interhemispheric communication, motor coordination, visual acuity, sensory integration, reading speed/comprehension, executive function, personality, and memory. We also identify neuroanatomic features underlying white matter degradation whose severity is associated with the male sex. Future studies should compare our findings to functional measures and other neurodegenerative processes.

Jan Brabec, Filip Szczepankiewicz, Finn Lennartsson, Elisabet Englund, Houman Pebdani, Johan Bengzon, Linda Knutsson, Carl-Fredrik Westin, Pia C Sundgren, and Markus Nilsson. 2022. . Neuroimage Clin, 33, Pp. 102912.

BACKGROUND: Preoperative radiological assessment of meningioma characteristics is of value for pre- and post-operative patient management, counselling, and surgical approach. PURPOSE: To investigate whether tensor-valued diffusion MRI can add to the preoperative prediction of meningioma consistency, grade and type. MATERIALS AND METHODS: 30 patients with intracranial meningiomas (22 WHO grade I, 8 WHO grade II) underwent MRI prior to surgery. Diffusion MRI was performed with linear and spherical b-tensors with b-values up to 2000 s/mm2. The data were used to estimate mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and its components-the anisotropic and isotropic kurtoses (MKA and MKI). Meningioma consistency was estimated for 16 patients during resection based on ultrasonic aspiration intensity, ease of resection with instrumentation or suction. Grade and type were determined by histopathological analysis. The relation between consistency, grade and type and dMRI parameters was analyzed inside the tumor ("whole-tumor") and within brain tissue in the immediate periphery outside the tumor ("rim") by histogram analysis. RESULTS: Lower 10th percentiles of MK and MKA in the whole-tumor were associated with firm consistency compared with pooled soft and variable consistency (n = 7 vs 9; U test, p = 0.02 for MKA 10 and p = 0.04 for MK10) and lower 10th percentile of MD with variable against soft and firm (n = 5 vs 11; U test, p = 0.02). Higher standard deviation of MKI in the rim was associated with lower grade (n = 22 vs 8; U test, p = 0.04) and in the MKI maps we observed elevated rim-like structure that could be associated with grade. Higher median MKA and lower median MKI distinguished psammomatous type from other pooled meningioma types (n = 5 vs 25; U test; p = 0.03 for MKA 50 and p = 0.03 and p = 0.04 for MKI 50). CONCLUSION: Parameters from tensor-valued dMRI can facilitate prediction of consistency, grade and type.

Yang Ji, W., Borjan Gagoski, Carl-Fredrik Westin, Yogesh Rathi, and Lipeng Ning. 2022. . Magn Reson Med, 87, 6, Pp. 2697-709.

PURPOSE: To accelerate the acquisition of relaxation-diffusion imaging by integrating time-division multiplexing (TDM) with simultaneous multi-slice (SMS) for EPI and evaluate imaging quality and diffusion measures. METHODS: The time-division multiplexing (TDM) technique and SMS method were integrated to achieve a high slice-acceleration (e.g., 6×) factor for acquiring relaxation-diffusion MRI. Two variants of the sequence, referred to as TDM3e-SMS and TDM2s-SMS, were developed to simultaneously acquire slice groups with three distinct TEs and two slice groups with the same TE, respectively. Both sequences were evaluated on a 3T scanner with in vivo human brains and compared with standard single-band (SB) -EPI and SMS-EPI using diffusion measures and tractography results. RESULTS: Experimental results showed that the TDM3e-SMS sequence with total slice acceleration of 6 (multiplexing factor (MP) = 3 × multi-band factor (MB) = 2) provided similar image intensity and microstructure measures compared to standard SMS-EPI with MB = 2, and yielded less bias in intensity compared to standard SMS-EPI with MB = 4. The three sequences showed a similar positive correlation between TE and mean kurtosis (MK) and a negative correlation between TE and mean diffusivity (MD) in white matter. Multi-fiber tractography also shows consistency of results in TE-dependent measures between different sequences. The TDM2s-SMS sequence (MP = 2, MB = 2) also provided imaging measures similar to standard SMS-EPI sequences (MB = 2) for single-TE diffusion imaging. CONCLUSIONS: The TDM-SMS sequence can provide additional 2x to 3x acceleration to SMS without degrading imaging quality. With the significant reduction in scan time, TDM-SMS makes joint relaxation-diffusion MRI a feasible technique in neuroimaging research to investigate new markers of brain disorders.

Fan Zhang, Alessandro Daducci, Yong He, Simona Schiavi, Caio Seguin, Robert E Smith, Chun-Hung Yeh, Tengda Zhao, and Lauren J O Donnell. 2022. . Neuroimage, 249, Pp. 118870.

Diffusion magnetic resonance imaging (dMRI) tractography is an advanced imaging technique that enables in vivo reconstruction of the brain’s white matter connections at macro scale. It provides an important tool for quantitative mapping of the brain’s structural connectivity using measures of connectivity or tissue microstructure. Over the last two decades, the study of brain connectivity using dMRI tractography has played a prominent role in the neuroimaging research landscape. In this paper, we provide a high-level overview of how tractography is used to enable quantitative analysis of the brain’s structural connectivity in health and disease. We focus on two types of quantitative analyses of tractography, including: 1) tract-specific analysis that refers to research that is typically hypothesis-driven and studies particular anatomical fiber tracts, and 2) connectome-based analysis that refers to research that is more data-driven and generally studies the structural connectivity of the entire brain. We first provide a review of methodology involved in three main processing steps that are common across most approaches for quantitative analysis of tractography, including methods for tractography correction, segmentation and quantification. For each step, we aim to describe methodological choices, their popularity, and potential pros and cons. We then review studies that have used quantitative tractography approaches to study the brain’s white matter, focusing on applications in neurodevelopment, aging, neurological disorders, mental disorders, and neurosurgery. We conclude that, while there have been considerable advancements in methodological technologies and breadth of applications, there nevertheless remains no consensus about the "best" methodology in quantitative analysis of tractography, and researchers should remain cautious when interpreting results in research and clinical applications.

S, Esra Abaci Turk, Mikhail Bessmeltsev, P, Justin Solomon, and Polina Golland. 2022. . IEEE Trans Med Imaging, 41, 4, Pp. 925-36.

We present a volumetric mesh-based algorithm for parameterizing the placenta to a flattened template to enable effective visualization of local anatomy and function. MRI shows potential as a research tool as it provides signals directly related to placental function. However, due to the curved and highly variable in vivo shape of the placenta, interpreting and visualizing these images is difficult. We address interpretation challenges by mapping the placenta so that it resembles the familiar ex vivo shape. We formulate the parameterization as an optimization problem for mapping the placental shape represented by a volumetric mesh to a flattened template. We employ the symmetric Dirichlet energy to control local distortion throughout the volume. Local injectivity in the mapping is enforced by a constrained line search during the gradient descent optimization. We validate our method using a research study of 111 placental shapes extracted from BOLD MRI images. Our mapping achieves sub-voxel accuracy in matching the template while maintaining low distortion throughout the volume. We demonstrate how the resulting flattening of the placenta improves visualization of anatomy and function. Our code is freely available at https://github.com/mabulnaga/placenta-flattening.