Non-invasive in-utero quantification of vascular reactivity in human placenta.

OBJECTIVE: Placental vascular reactivity (PlVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders alter the characteristics of PlVR, resulting in suboptimal oxygen delivery, although current understanding is limited by the lack of non-invasive, repeatable methods to measure PlVR in utero. Our objective was to quantify PlVR by measuring the placental response to transient changes in maternal carbon dioxide (CO2) using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI). We hypothesized that PlVR will increase with gestational age to meet the changing demands of a growing fetus, and that PlVR will be driven by a maternal response to changes in CO2 concentration. METHODS: This was a cross-sectional study of 35 women with a healthy singleton pregnancy, of whom 31 were included in the analysis. The median gestational age was 32.6 (range, 22.6-38.4) weeks. Pregnant women were instructed to follow audiovisual breathing cues during a MRI scan. Maternal end-tidal CO2 (EtCO2) was measured concurrently with resting placental BOLD MRI for a total of 7-8 min. Preprocessing of magnetic resonance images consisted of manual delineation of placental anatomy and motion correction. In each placental voxel, vascular reactivity was computed using a coherence-weighted general linear model between MRI signal and EtCO2 stimulus. Global PlVR was computed as the mean of voxel-wise PlVR values across the placenta. RESULTS: PlVR, quantified by the placental response to induced, transient changes in maternal CO2, was consistently measured in utero using BOLD MRI. PlVR increased non-linearly with advancing gestational age (P < 0.001) and was higher on the fetal side of the placenta. PlVR was associated positively with fetal brain volume after accounting for gestational age. PlVR did not show any significant associations with maternal characteristics. CONCLUSIONS: We present, for the first time, a non-invasive paradigm to quantify PlVR in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that PlVR is driven by a fetal response to changes in maternal CO2. Ease of translation to the clinical setting makes PlVR a promising biomarker for the identification and management of high-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The carbon partitioning of glucose and DIC in mixotrophic, heterotrophic and photoautotrophic cultures of Tetraselmis suecica.

OBJECTIVE: Changes in the partitioning of dissolved inorganic (DIC) and glucose were elucidated by utilising 13C labelled DIC or glucose, and quantifying the biochemical profile of mixotrophic, heterotrophic and photoautotrophic cultures of the microalga Tetraselmis suecica. RESULTS: Mixotrophic cultivation increases microalgal productivity and changes their biochemical profile, due to an alteration in the partitioning of carbon within the cell. When cultured mixotrophically and heterotrophically, there is enhanced incorporation of carbon into shorter chain saturated fatty acids and non-lipid biomass, compared to photoautotrophic cultivation. Autotrophic culture results in increased total fatty acid content of cultures (4.19% dry weight compared to 2.13%) and shifts the fatty acid profile in favour of long-chain unsaturated fatty acids, such as 18:2 n-(9,12), compared to mixotrophic culture. Quantifying the changes in partitioning between DIC and glucose facilitates tailoring of the biochemical profile to develop "designer" algae. CONCLUSIONS: There is a condition specific shift in carbon partitioning into different fatty acid and biochemical fractions in T. suecica, with more inorganic carbon partitioned into 18:2 n-(9,12) in photoautotrophic rather than mixotrophic cultures.

Bisphosphonate therapy in an infant with generalized arterial calcification with an ABCC6 mutation.

Generalized arterial calcification of infancy (GACI) is a rare genetic disorder with high infantile mortality, described to be due to ENPP1, and less commonly ABCC6 mutations. Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Without therapy, patients will die before 6 months of age. Our patient is now 3 years old, former recipient twin of twin-to-twin transfusion syndrome (TTTS). Initial fetal echocardiogram at 19 weeks showed calcifications of the ascending aorta and pulmonary artery (PA). She underwent utero laser therapy, and despite resolution of the TTTS, her follow-up scans showed progressive calcification of the aorta and PA. Postnatal echocardiogram showed calcification and supravalvar stenosis of the aorta and PA. CT on day of life 6 showed calcifications in the PAs, aortic arch, and descending aorta. Quantification of valvular calcification can be difficult; in our patient, increasing outflow tract gradient on echocardiogram was used to monitor disease progression. Molecular testing revealed an ABCC6 gene mutation. She was started on weekly IV pamidronate (0.1-0.3 mg/kg/week) on day 8 of life then transitioned to oral etidronate (15-20 mg/kg/day). Given progressive supravalvar aortic and pulmonary stenosis, she underwent surgical repair with patch augmentation of the PA and ascending aorta at 4 months old. She has done well post-operatively, continuing on enteral bisphosphonate therapy with no side effects to date. Her identical twin was confirmed to have the same mutation and remains asymptomatic with no calcifications. Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Echocardiographic evaluation can be used to monitor disease progression by arterial gradients. Molecular testing is also essential to evaluate for possible co-morbidities in these patients and pregnancy management for the future.

Cortical differences in diverticular disease and correlation with symptom reports.

BACKGROUND: Recent studies have shown that the brain of patients with gastrointestinal disease differ both structurally and functionally from that of controls. Highly somatizing diverticular disease (HSDD) patients were also shown to differ from low somatizing (LSDD) patients functionally. This study aimed to investigate how they differed structurally. METHODS: Four diseases subgroups were studied in a cross-sectional design: 20 patients with asymptomatic diverticular disease (ADD), 18 LSDD, 16 HSDD, and 18 with irritable bowel syndrome. We divided DD patients into LSDD and HSDD using a cutoff of 6 on the Patient Health Questionnaire 12 Somatic Symptom (PHQ12-SS) scale. All patients underwent a 1-mm isotropic structural brain MRI scan and were assessed for somatization, hospital anxiety, depression, and pain catastrophizing. Whole brain volumetry, cortical thickness analysis and voxel-based morphometry were carried out using Freesurfer and SPM. KEY RESULTS: We observed decreases in gray matter density in the left and right dorsolateral prefrontal cortex (dlPFC), and in the mid-cingulate and motor cortex, and increases in the left (19, 20) and right (19, 38) Brodmann Areas. The average cortical thickness differed overall across groups (P = .002) and regionally: HSDD > ADD in the posterior cingulate cortex (P = .03), HSDD > LSDD in the dlPFC (P = .03) and in the ventrolateral PFC (P < .001). The thickness of the anterior cingulate cortex and of the mid-prefrontal cortex were also found to correlate with Pain Catastrophizing (Spearman's ρ = 0.24, P = .043 uncorrected and Spearman's ρ = 0.25, P = .03 uncorrected). CONCLUSION & INFERENCES: This is the first study of structural gray matter abnormalities in diverticular disease patients. The data show brain differences in the pain network.

Metabolic and reproductive characteristics of replacement beef heifers subjected to an early-weaning regimen involving high-concentrate feeding.

In an effort to better understand the consequences of early weaning (EW) for replacement beef heifers, a two-phase experiment was conducted investigating the impact on metabolic function and documenting reproductive characteristics. In phase 1, Angus×Simmental heifers (n=35) were stratified by BW and sire, and randomly assigned to either a normal weaning (NW, n=18) or EW (n=17) treatment. EW heifers were weaned at 107±3 days of age and provided access to a concentrate-based ration ad libitum with limit-fed mixed grass hay. NW heifers remained with their dams until 232±3 days of age, at which point heifers from both treatments were comingled and grazed on mixed summer pasture. Following NW, weekly blood samples were collected from all heifers for progesterone analyses used to determine the onset of puberty. Pelvic and ovarian size was measured before breeding. All heifers were subjected to an estrous synchronization protocol with timed artificial insemination (AI) at 437±4 days of age. During phase 2 of the experiment, a subset of pregnant heifers (n=16) were divided into two replicates and subjected to a glucose tolerance test, epinephrine challenge and progesterone clearance analysis. Neither age nor BW at puberty differed between EW and NW heifers. Likewise, no differences in pelvic area or ovarian size were observed. Thus, it appears that the reproductive maturity of EW and NW heifers was similar. Heifers studied during phase 2 of the experiment were restricted to those that had become pregnant to their first AI. Within this cohort, EW heifers tended to have lower overall circulating progesterone concentrations than those that were NW (P=0.14). Aspects of glucose and insulin dynamics were also altered, as EW heifers tended to have lower baseline glucose concentrations (P=0.10) despite similar baseline insulin concentrations. Compared with NW heifers, EW heifers had lower insulin area under the curve (P<0.05), which was partly the result of a tendency for lower peak insulin concentrations (P=0.11). Results of the glucose tolerance test indicate that a lesser insulin response was necessary to properly clear the glucose in the EW heifers, suggesting enhanced insulin sensitivity. Collectively, these results indicate that EW is not detrimental for the growth or reproductive development of replacement beef heifers, although some differences in glucose and insulin dynamics persist into adulthood.

Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: A Markov decision analysis.

BACKGROUND: Neoadjuvant therapy is gaining acceptance as a valid treatment option for borderline resectable pancreatic cancer; however, its value for clearly resectable pancreatic cancer remains controversial. The aim of this study was to use a Markov decision analysis model, in the absence of adequately powered randomized trials, to compare the life expectancy (LE) and quality-adjusted life expectancy (QALE) of neoadjuvant therapy to conventional upfront surgical strategies in resectable pancreatic cancer patients. METHODS: A Markov decision model was created to compare two strategies: attempted pancreatic resection followed by adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy followed by restaging with, if appropriate, attempted pancreatic resection. Data obtained through a comprehensive systematic search in PUBMED of the literature from 2000 to 2015 were used to estimate the probabilities used in the model. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Of the 786 potentially eligible studies identified, 22 studies met the inclusion criteria and were used to extract the probabilities used in the model. Base case analyses of the model showed a higher LE (32.2 vs. 26.7 months) and QALE (25.5 vs. 20.8 quality-adjusted life months) for patients in the neoadjuvant therapy arm compared to upfront surgery. Probabilistic sensitivity analyses for LE and QALE revealed that neoadjuvant therapy is favorable in 59% and 60% of the cases respectively. CONCLUSION(S): Although conceptual, these data suggest that neoadjuvant therapy offers substantial benefit in LE and QALE for resectable pancreatic cancer patients. These findings highlight the value of further prospective randomized trials comparing neoadjuvant therapy to conventional upfront surgical strategies.

Anticipation of thermal pain in diverticular disease.

BACKGROUND: The relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients. METHODS: Gastrointestinal symptoms and somatization were evaluated via the Patient Health Question-12 Somatic Symptom and the SDD group divided into low (≤6 [LSDD]) and high (≥7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the 'cued' anticipatory phase was performed. KEY RESULTS: Within the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups. CONCLUSIONS & INFERENCES: The HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.

Assessment of fetal cardiomyopathy in early-stage twin-twin transfusion syndrome: comparison between commonly reported cardiovascular assessment scores.

OBJECTIVES: To assess the relationship between commonly reported fetal cardiomyopathy scoring systems in early-stage twin-twin transfusion syndrome (TTTS). METHODS: We reviewed retrospectively 100 cases of Quintero Stages I and II TTTS referred to our center for evaluation from 2008 to 2010. The cases were divided into groups of 25, representing each of four grades of TTTS cardiomyopathy as assessed by Cincinnati stage: no cardiomyopathy, Stage IIIa, Stage IIIb and Stage IIIc. Spearman correlation (rs ) was calculated between the Children's Hospital of Philadelphia (CHOP) score, cardiovascular profile score (CVPS), Cincinnati stage and myocardial performance index (MPI). RESULTS: There was a weak correlation between the Cincinnati stage and the CHOP score (rs = 0.36) and CVPS (rs = -0.39), while correlation was strong between the CHOP score and CVPS (rs = -0.72). MPI elevation was concordant with Cincinnati stage more frequently (82% of cases) than were ventricular hypertrophy (43%) or atrioventricular valve regurgitation (28%). 51% of fetuses with minimally elevated CHOP score (0-1) and 48% of fetuses with minimally depressed CVPS (9-10) had significant elevation (Z-score ≥ +3) in right ventricular or left ventricular MPI. CONCLUSIONS: MPI has a strong influence on grading the severity of fetal cardiomyopathy using the Cincinnati stage among fetuses with mild TTTS. Furthermore, significant elevation of the MPI is common among fetuses with mild disease as assessed by the CHOP score and CVPS. These differences should be understood when assessing and grading cardiomyopathy in TTTS, particularly in early (Quintero Stages I and II) disease.

Leptospirosis following a major flood in Central Queensland, Australia.

Throughout December 2010 and January 2011, Queensland experienced widespread flooding due to unusually protracted and heavy rainfalls. In mid-January 2011, four individuals from a small community in Central Queensland were hospitalized with leptospirosis. A further five cases were subsequently identified from around Central Queensland, bringing the total to nine. Microscopic agglutination testing found that serovar Arborea (Leptospira borgpetersenii serovar Arborea) was presumptively responsible for leptospirosis in seven of nine confirmed cases. Serovars Hardjo and Australis were identified in samples from two remaining cases. All cases had exposure to flood water. No single exposure source was identified. This is the first reported outbreak of leptospirosis in Central Queensland and the first report of leptospirosis cases associated with flood water inundation in Queensland. Public health authorities should continue to promote awareness of leptospirosis in flood-affected populations. Healthcare providers must maintain a high level of suspicion for leptospirosis during and after flood events.

Study of two-neutron radioactivity in the decay of 26O.

A new technique was developed to measure the lifetimes of neutron unbound nuclei in the picosecond range. The decay of 26O→24O+n+n was examined as it had been predicted to have an appreciable lifetime due to the unique structure of the neutron-rich oxygen isotopes. The half-life of 26O was extracted as 4.5(-1.5)(+1.1)(stat)±3(syst) ps. This corresponds to 26O having a finite lifetime at an 82% confidence level and, thus, suggests the possibility of two-neutron radioactivity.

First observation of ground state dineutron decay: 16Be.

We report on the first observation of dineutron emission in the decay of 16Be. A single-proton knockout reaction from a 53 MeV/u 17B beam was used to populate the ground state of 16Be. 16Be is bound with respect to the emission of one neutron and unbound to two-neutron emission. The dineutron character of the decay is evidenced by a small emission angle between the two neutrons. The two-neutron separation energy of 16Be was measured to be 1.35(10) MeV, in good agreement with shell model calculations, using standard interactions for this mass region.

Exploring the low-Z shore of the island of inversion at n=19.

The technique of invariant mass spectroscopy has been used to measure, for the first time, the ground state energy of neutron-unbound (28)F, determined to be a resonance in the (27)F+n continuum at 220(50) keV. States in (28)F were populated by the reactions of a 62 MeV/u (29)Ne beam impinging on a 288 mg/cm(2) beryllium target. The measured (28)F ground state energy is in good agreement with USDA/USDB shell model predictions, indicating that pf shell intruder configurations play only a small role in the ground state structure of (28)F and establishing a low-Z boundary of the island of inversion for N=19 isotones.

Effect of ribavirin on junin virus infection in guinea pigs.

Junin virus (JUNV) is the aetiological agent of Argentine haemorrhagic fever. The pathogenesis of the infection is not well understood, no licensed vaccines exist and no specific antiviral therapy is available. Previous studies have demonstrated the ability of ribavirin to delay and reduce JUNV disease and virus burden in guinea pigs without preventing death. Based on available data, we performed three different studies to determine the efficacy of ribavirin against JUNV in the guinea pig model with a focus on survival. Different doses and treatment schedules of ribavirin were tested in a lethal model of JUNV infection. Our results show that prolonged treatment with high doses of ribavirin significantly reduces the mortality in guinea pigs infected with JUNV. These results may be useful in future experimental studies or clinical testing.

Unresolved question of the 10He ground state resonance.

The ground state of (10)He was populated using a 2p2n-removal reaction from a 59 MeV/u (14)Be beam. The decay energy of the three-body system, (8)He+n+n, was measured and a resonance was observed at E=1.60(25) MeV with a 1.8(4) MeV width. This result is in agreement with previous invariant mass spectroscopy measurements, using the (11)Li(-p) reaction, but is inconsistent with recent transfer reaction results. The proposed explanation that the difference, about 500 keV, is due to the effect of the extended halo nature of (11)Li in the one-proton knockout reaction is no longer valid as the present work demonstrates that the discrepancy between the transfer reaction results persists despite using a very different reaction mechanism, (14)Be(-2p2n).

Patterns of estrous cycles, estrous behavior, and circulating prolactin in spring and summer in ewes selected for autumn lambing and exposed to ambient or long-day photoperiods.

Estrous behavior in response to ambient and long-day photoperiods was evaluated in ewes developed by 10 years of selection for ability to lamb in autumn. Following October lambing, 67 ewes were moved indoors and exposed to long-day (16L:8D) or ambient photoperiods from February 2 until July 6. Two vasectomized rams with marking harnesses were housed with each group. Estrous behavior was monitored twice weekly. Ewes from the selection line were unresponsive to long days, with no effects on estrous behavior, frequency of ovulation, or circulating prolactin. Adult ewes were anestrus for only 34±3 d, but 2- and 3-years-old ewes were anestrus for 72±7 and 57±10 d, respectively. Frequencies of ovulation based on circulating progesterone concentrations in March, May, and June were 97%, 95% and 52%, respectively, indicating that many ewes that did not exhibit estrus still ovulated. Prolactin concentrations increased from 10 ng/ml in February to 27 ng/ml in March and 173 ng/ml in June but were not affected by light treatment. Ten ewes that failed to exhibit estrus behavior for at most 24 d during the main study were then monitored for 74 additional long days. Nine of 10 ewes did not exhibit estrus for periods similar to 1 or 2 estrus cycles during this period, but eight ewes re-initiated cycles by the end of the study on September 18. Selection for ability to lamb in autumn thus resulted in ewes with an abbreviated seasonal anestrus and reduced sensitivity to long days.

fMRI and MEG analysis of visceral pain in healthy volunteers.

BACKGROUND: Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis. METHODS: Liminal and painful rectal barostat balloon inflation thresholds were assessed in 14 female healthy volunteers. Subliminal, liminal and painful 40s periods of distension were applied in a pseudo-randomized paradigm during fMRI and MEG neuroimaging. Functional MRI data analysis was performed comparing standard box-car models of the full 40s of stimulus (Block) with models of the inflation (Ramp-On) and deflation (Ramp-Off) of the barostat. Similar models were used in MEG analysis of oscillatory activity. KEY RESULTS: Modeling the data using a standard Block analysis failed to detect areas of interest found to be active using Ramp-On and Ramp-Off models. Ramp-On generated activity in anterior insula and cingulate regions and other pain-matrix associated areas. Ramp-Off demonstrated activity of a network of posterior insula, SII and posterior cingulate. Active areas were consistent with those identified from MEG data. CONCLUSIONS & INFERENCES: In studies of visceral pain, fMRI model design strongly influences the detected activity and must be accounted for to effectively explore the fMRI data in healthy subjects and within patient groups. In particular a strong cortical response is detected to inflation and deflation of the barostat, rather than to its absolute volume.

Aerobic fitness and obesity: relationship to cerebral white matter integrity in the brain of active and sedentary older adults.

OBJECTIVE: Aerobic fitness (VO(2) peak) and obesity risk (OR) may impact brain health. This study examined hemispheric and segment specific relationships between VO(2) peak, OR and cerebral white-matter (CWM) integrity in the cingulum brain region in healthy older adults. METHODS: Fifteen subjects (66±6 years) completed VO(2) peak testing and MRI of the brain. OR was determined via body mass index (BMI) and abdominal girth. MRI analysis was performed with a structural 3D T1 MP-Rage and diffusion tensor imaging technique (DTI, 21 directions, repeated four times) on a 3.0 T MR imaging unit. CWM integrity indices, fractional anisotropy (FA) and mean diffusivity (MD), were computed from the tensors. The anterior, middle and posterior cingulum segments were analysed on both sides of the brain. Partial correlations (age and gender controlled) and standard multiple regressions were used to determine significant associations and unique contributions to CWM integrity. RESULTS: VO(2) peak was moderately related to FA in the left middle cingulum segment (r partial=0.573, p=0.041) and explained 28.5% of FA's total variance (p=0.10). Abdominal girth (r partial=-0.764, p=0.002) and BMI (r partial=-0.690, p=0.009) were inversely related to FA in the right posterior cingulum (RPC) segment. Abdominal girth and BMI uniquely explained 53.9% of FA's total variance (p=0.012) and 43.9% (p=0.040), respectively, in the RPC. CONCLUSION: Higher aerobic fitness and lower obesity risk are related to greater CWM integrity but not in the same cingulum segments.

The effect of exercise on the cerebral vasculature of healthy aged subjects as visualized by MR angiography.

BACKGROUND AND PURPOSE: Prior studies suggest that aerobic exercise may reduce both the brain atrophy and the decline in fractional anisotropy observed with advancing age. It is reasonable to hypothesize that exercise-induced changes to the vasculature may underlie these anatomic differences. The purpose of this blinded study was to compare high-activity and low-activity healthy elderly volunteers for differences in the cerebrovasculature as calculated from vessels extracted from noninvasive MR angiograms (MRAs). MATERIALS AND METHODS: Fourteen healthy elderly subjects underwent MRA. Seven subjects reported a high level of aerobic activity (64 +/- 5 years of age; 5 men, 2 women) and 7, a low activity level (68 +/- 6 years of age; 5 women, 2 men). Following vessel segmentation from MRA by an individual blinded to subject activity level, quantitative measures of vessel number, radius, and tortuosity were calculated and histogram analysis of vessel number and radius was performed. RESULTS: Aerobically active subjects exhibited statistically significant reductions in vessel tortuosity and an increased number of small vessels compared with less active subjects. CONCLUSIONS: Aerobic activity in elderly subjects is associated with lower vessel tortuosity values and an increase in the number of small-caliber vessels. It is possible that an aerobic exercise program may contribute to healthy brain aging. MRA offers a noninvasive approach to visualizing the cerebral vasculature and may prove useful in future longitudinal investigations.

Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease.

BACKGROUND AND PURPOSE: It is not possible to determine if neonates diagnosed with Krabbe disease through statewide neonate screening programs will develop the disease as infants, juveniles, or adults. The only available treatment for this fatal neurodegenerative condition is unrelated umbilical cord transplantation, but this treatment is only effective before clinical symptoms appear. Therefore, a marker of disease progression is needed. The purpose of this study was to evaluate the use of diffusion tensor imaging (DTI) with fiber tracking in identifying early changes in major motor tracts of asymptomatic neonates with infantile Krabbe disease. MATERIALS AND METHODS: Six neonates with infantile Krabbe disease identified because of family history underwent brain MR imaging within the first 4 weeks of life. Six-direction DTI and quantitative tractography of the corticospinal tracts were performed. Hypothesis tests, 1 for each hemisphere, were used to determine whether the fractional anisotropy (FA) ratio of the neonates with infantile Krabbe disease was significantly different from that of 45 age- and sex-matched controls. RESULTS: The average FA ratio for patients with Krabbe disease was 0.89 and 0.87 for left and right tracts, respectively (P = .002 and < .001). After adjusting for gestational age, gestational age at birth, birth weight, sex, and race, the 6 patients with Krabbe disease had significantly lower FA values than the controls (P < .001). CONCLUSIONS: DTI with quantitative tractography detected significant differences in the corticospinal tracts of asymptomatic neonates who had the early-onset form of Krabbe disease. Once standardized and validated, this tool has the potential to be used as a marker of disease progression in neonates diagnosed through statewide neonate screening programs.