Fluid intelligence is associated with cortical volume and white matter tract integrity within multiple-demand system across adult lifespan.

BACKGROUND: Fluid intelligence (Gf) is the innate ability of an individual to respond to complex and unexpected situations. Although some studies have considered that the multiple-demand (MD) system of the brain was the biological foundation for Gf, further characterization of their relationships in the context of aging is limited. The present study hypothesized that the structural metrics of the MD system, including cortical thickness, cortical volumes, and white matter (WM) tract integrity, was the brain correlates for Gf across the adult life span. Partial correlation analysis was performed to investigate whether the MD system could still explain Gf independent of the age effect. Moreover, the partial correlations between Gf and left/right structural metrics within the MD regions were compared to test whether the correlations displayed distinct lateralization. METHODS: The participants were recruited from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) databank, comprising the images of 603 healthy participants aged 18-88 years acquired on a 3-T system. The MRI data included high-resolution T1-weighted and diffusion-weighted images, from which gray matter and WM structural metrics of the MD system were analyzed, respectively. The structural metrics of gray matter were quantified in terms of cortical volume/thickness of five pairs of cortical regions, and those of WM were quantified in terms of the mean axial diffusivity (DA), radial diffusivity (DR), mean diffusivity (DM), and generalized fractional anisotropy (GFA) on five pairs of tracts. Partial correlation controlling for age and sex effects, was performed to investigate the associations of Gf scores with the mean DA, DR, DM and GFA of all tracts in the MD system, those of left and right hemispheric tracts, and those of each tract. Fisher's exact test was used to compare the partial correlations between left and right MD regions. RESULTS: The linear relationship between cortical volumes and Gf was evident across all levels of the MD system even after controlling for age and sex. For the WM integrity, diffusion indices including DA, DR, DM and GFA displayed linear relationships with Gf scores at various levels of the MD system. Among the 10 WM tracts connecting the MD regions, bilateral superior longitudinal fasciculus I and bilateral frontal aslant tracts exhibited the strongest and significant associations. Our results did not show significant inter-hemispheric differences in the associations between structural metrics of the MD system and Gf. CONCLUSION: Our results demonstrate significant associations between Gf and both cortical volumes and tract integrity of the MD system across the adult lifespan in a population-based cohort. We found that the association remained significant in the entire adult lifespan despite simultaneous decline of Gf and the MD system. Our results suggest that the MD system might be a structural underpinning of Gf and support the fronto-parietal model of cognitive aging. However, we did not find hemispheric differences in the Gf-MD correlations, not supporting the hemi-aging hypothesis.

Gene therapy improves brain white matter in aromatic l-amino acid decarboxylase deficiency.

OBJECTIVE: Children with aromatic l-amino acid decarboxylase (AADC) deficiency suffer from severe motor dysfunction. Restoration of dopamine levels in the putamen by gene therapy has led to significant improvement in motor function. This study explored brain structure changes in patients. METHODS: Brain diffusion tensor imaging (DTI) was performed before and 12 months after gene therapy. Whole-brain tract-specific analysis was performed to assess white matter microstructural integrity. RESULTS: In the 8 patients (aged 1.67-8.42 years) enrolled in the study, gene therapy did not affect macroscopic structure. DTI before gene therapy revealed lower total mean fractional anisotropy (FA) values in patients than in the age-matched pretreatment controls (p = 0.017; median difference = -0.0136; 95% confidence interval [CI] [-0.0319, -0.0126]). After gene therapy, total mean FA increased (p = 0.012, median difference = 0.0211, 95% CI [0.0094, 0.0456]), and the values in the patients were not different from the age-matched posttreatment controls. Increase in total mean FA after gene therapy in patients was correlated with their increase in motor score (r = 0.846; p = 0.008), but was inversely correlated with their ages at the time of gene therapy (r = -0.754; p = 0.031). Corticospinal tracts, and the thalamic radiation and callosal fibers involving motor function, improved after gene therapy. INTERPRETATION: Improvement in the microstructural integrity of white matter tracts is associated with the improvement in motor function following gene therapy. Ann Neurol 2019;85:644-652.

Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints.

Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.

Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception.

Although the small-diameter primary afferent fibers in the skin promptly respond to nociceptive stimuli and convey sensory inputs to the central nervous system, the neural signatures that underpin the relationship between cutaneous afferent fibers and pain perception remain elusive. We combined skin biopsy at the lateral aspect of the distal leg, which is used to quantify cutaneous afferent fibers, with fMRI, which is used to assess brain responses and functional connectivity, to investigate the relationship between cutaneous sensory nerves and the corresponding pain perception in the brain after applying heat pain stimulation to the dorsum of the right foot in healthy subjects. During painful stimulation, the degree of cutaneous innervation, as measured by epidermal nerve fiber density, was correlated with individual blood oxygen level-dependent (BOLD) signals of the posterior insular cortex and of the thalamus, periaqueductal gray, and rostral ventromedial medulla. Pain perception was associated with the activation of the anterior insular cortex and with the functional connectivity from the anterior insular cortex to the primary somatosensory cortex during painful stimulation. Most importantly, both epidermal nerve fiber density and activity in the posterior insular cortex showed a positive correlation with the strength of coupling under pain between the anterior insular cortex and the primary somatosensory cortex. Thus, our findings support the notion that the neural circuitry subserving pain perception interacts with the cerebral correlates of peripheral nociceptive fibers, which implicates an indirect role for skin nerves in human pain perception.

MRI evaluation of the adaptive response of the contralateral kidney following nephrectomy in patients with renal cell carcinoma.

PURPOSE: To study the adaptive responses of the contralateral kidney and its association with renal outcome in patients with renal cell carcinoma (RCC) following radical nephrectomy (RN). MATERIALS AND METHODS: Eleven patients with RCC scheduled for RN and 15 control patients scheduled for adrenalectomy (Control) were prospectively recruited. All subjects underwent 4 MRI studies: 1 before surgery and 3 at 1 week, 1 month and 3 months after surgery, respectively. T2-weighted imaging and dynamic contrast-enhanced imaging were performed to estimate the renal volume and renal blood flow (RBF) of the contralateral kidney, respectively. The patients' serum creatinine levels were examined to determine the estimated glomerular filtration rate (e-GFR). The changes in renal volume at 3 months and both RBF and e-GFR during the serial follow-up were compared and associations between both of them were measured in both groups. RESULTS: In the RN group, RBF increased at 1 week (2.78 ± 0.93 mL/min/g, P = 0.002) and 1 month (2.65 ± 0.85 mL/min/g, P = 0.002), compared with presurgical values (1.94 ± 0.61 mL/min/g), and it returned to presurgical levels at 3 months (2.11 ± 0.73 mL/min/g, P = 0.432). In contrast, e-GFR decreased at 1 week (56.4 ± 20.3 mL/min/1.73 m(2) , P = 0.049) and 1 month (52.4 ± 18.8 mL/min/1.73 m(2) , P = 0.027), compared with presurgical values (66.3 ± 18.3 mL/min/1.73 m(2) ), and it returned to presurgical levels at 3 months (73.3 ± 29.5 mL/min/1.73 m(2) , P = 0.496). The renal volume increased at 3 months compared with baseline (198 ± 87 versus 329 ± 175 mL, P < 0.001). The change in renal volume was correlated with the change in RBF at 1 week (r = 0.609, P = 0.047). CONCLUSION: In patients with RCC following RN, an early increase in RBF of the contralateral kidney is associated with late renal hypertrophy which might normalize glomerular hyperfiltration and restore renal function.

Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/ hyperactivity disorder.

BACKGROUND: The neural substrate for clinical symptoms and neuropsychological performance in individuals with attention-deficit/hyperactivity disorder (ADHD) has rarely been studied and has yielded inconsistent results. We sought to compare the microstructural property of fibre tracts associated with the prefrontal cortex and its association with ADHD symptoms and a wide range of attention performance in youth with ADHD and healthy controls. METHODS: We assessed youths with ADHD and age-, sex-, handedness-, coil- and intelligence-matched controls using the Conners' Continuous Performance Test (CCPT) for attention performance and MRI. The 10 target tracts, including the bilateral frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging tractography. We computed generalized fractional anisotropy (GFA) values to indicate tract-specific microstructural property. RESULTS: We included 50 youths with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in the left frontostriatal tracts, bilateral SLF and right cingulum bundle and performed worse in the CCPT than controls. Furthermore, alteration of the right SLF GFA was most significantly associated with the clinical symptom of inattention in youths with ADHD. Finally, youths with ADHD had differential association patterns of the 10 fibre tract GFA values with attention performance compared with controls. LIMITATIONS: Ten of the youths with ADHD were treated with methylphenidate, which may have long-term effects on microstructural property. CONCLUSION: Our study highlights the importance of the SLF, cingulum bundle and frontostriatal tracts for clinical symptoms and attention performance in youths with ADHD and demonstrates the involvement of different fibre tracts in attention performance in these individuals.

Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer's disease: a diffusion spectrum imaging study.

Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.

fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations.

Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes.

Contrast-enhanced MRI index of diffuse myocardial fibrosis is increased in primary aldosteronism.

PURPOSE: To assess the degree of myocardial fibrosis in patients with primary aldosteronism (PA). MATERIALS AND METHODS: Twenty-five patients with PA and 12 age-matched healthy volunteers underwent cine and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) on a 1.5 T MR system. From volume-time curves of cine MRI, the time for deceleration (Tdec) was determined to assess the left ventricle (LV) chamber stiffness. Based on phase-sensitive reconstructed LGE images, a fibrosis index called enhancement value (EV) was computed as the signal intensity change in the myocardium over blood before and after contrast. Both Tdec and EV were compared between patients and controls. The association between Tdec and EV was investigated. RESULTS: Patients showed a significantly higher EV (0.43 ± 0.05 vs. 0.36 ± 0.07; P = 0.002) and a significantly shorter Tdec (11.5 ± 3.5 %RR vs. 15.3 ± 2.4 %RR; P = 0.004) than controls. Significant correlations between EV and Tdec were observed in patients (r = -0.46, P = 0.018), in controls (r = -0.68, P = 0.015) and in all subjects (r = -0.63, P < 0.001). CONCLUSION: The fibrosis index is increased in patients with PA and the increase imposes an adverse effect on LV diastolic function.

Dynamic contrast-enhanced MRI in advanced nonsmall-cell lung cancer patients treated with first-line bevacizumab, gemcitabine, and cisplatin.

PURPOSE: To investigate dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of advanced nonsmall-cell lung cancer (NSCLC) patients treated with the antiangiogenic agent bevacizumab combined with gemcitabine and cisplatin as first-line treatment. MATERIALS AND METHODS: All patients were enrolled for MRI and computed tomography (CT) before and after the first three courses of bevacizumab combination chemotherapy. Pharmacokinetic parameters (K(trans), k(ep), v(e), v(p)) derived from DCE MRI were computed for the main mass. Parametric histogram analysis was obtained to evaluate changes of the internal tumor composition and for correlation with tumor response measured on CT. RESULTS: After three cycles of treatment, 11 patients showed decreased tumor size and a decreased value of all MR-derived pharmacokinetic parameters. Among these parameters, there was a significant decrease of mean and standard deviation of the K(trans) histogram as well as a decrease of mean of the k(ep) histogram (P < 0.05). Tumors with larger mean values of rate constant k(ep) (P < 0.0001) and smaller standard deviation of volume of extravascular extracellular space fraction v(e) (P < 0.0001) on histograms before chemotherapy were considered predictors for treatment response. CONCLUSION: DCE MRI enables a functional analysis of the treatment response of NSCLC. MRI parametric histogram has the potential to predict early treatment response of combined bevacizumab, gemcitabine, and cisplatin.

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization. Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention. Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period. Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline. Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Detecting blood-brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: a correlation study with contrast-enhanced MRI.

Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood-brain barrier, and the blood-brain barrier disruption can be detected by contrast-enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 µL/kg), and contrast-enhanced T1-weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time-weighted and susceptibility-weighted images were acquired. Volume-of-interest-based and threshold-based analyses were performed to quantify the contrast enhancement, which was then correlated with the ultrasound contrast agent dose and with the amount of Evans blue extravasation. Both effective transverse relaxation time-weighted and susceptibility-weighted images did not detect histology-proved intracranial hemorrhage at 10 µL/kg, but MRI failed to detect mild intracranial hemorrhage at 30 µL/kg. All tested sequences showed detectable contrast enhancement increasing with ultrasound contrast agent dose. In correlating with Evans blue extravasation, the gradient echo sequence was slightly better than the spin echo sequence and was comparable to longitudinal relaxation rate mapping. In conclusion, both gradient echo and spin echo sequences were all reliable in indicating the degree of focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage.

Exercise training increases myocardial perfusion in residual viable myocardium within infarct zone.

PURPOSE: To study the effect of exercise training on the myocardial perfusion in the postinfarct myocardium. MATERIALS AND METHODS: Twenty-nine patients with stable chronic myocardial infarction were randomly assigned to either a training group (N = 17) or a control group (N = 12). The training group received a 3-month exercise program. Cardiovascular MR was first performed before the training to establish a baseline, and subsequently performed once again upon conclusion of the program. Late gadolinium enhancement was used both to define the infarct and remote zones and to quantify the ratio of the residual viable myocardium (VMR) within the infarct zone. The myocardium was divided into subendocardial and subepicardial layers with equal thickness. The interval change of myocardial perfusion reserve (MPR) was computed for each zone and layer. The association between the exercise-induced perfusion change and VMR was analyzed for layers of the infarct zone. RESULTS: In the training group, the remote zone showed significantly increased MPR. The infarct zone showed no perfusion change in the subendocardial layer, but it demonstrated significantly increased MPR in the subepicardial layer. In the infarct zone, the change in MPR was associated with VMR. CONCLUSION: In chronic myocardial infarction, the exercise-induced perfusion change in the infarct zone is proportional to the amount of residual viable myocardium.

Differential Associations of White Matter Brain Age With Language-Related Mechanisms in Word-Finding Ability Across the Adult Lifespan.

Research on cognitive aging has established that word-finding ability declines progressively in late adulthood, whereas semantic mechanism in the language system is relatively stable. The aim of the present study was to investigate the associations of word-finding ability and language-related components with brain aging status, which was quantified by using the brain age paradigm. A total of 616 healthy participants aged 18-88 years from the Cambridge Centre for Ageing and Neuroscience databank were recruited. The picture-naming task was used to test the participants' language-related word retrieval ability through word-finding and word-generation processes. The naming response time (RT) and accuracy were measured under a baseline condition and two priming conditions, namely phonological and semantic priming. To estimate brain age, we established a brain age prediction model based on white matter (WM) features and estimated the modality-specific predicted age difference (PAD). Mass partial correlation analyses were performed to test the associations of WM-PAD with the cognitive performance measures under the baseline and two priming conditions. We observed that the domain-specific language WM-PAD and domain-general WM-PAD were significantly correlated with general word-finding ability. The phonological mechanism, not the semantic mechanism, in word-finding ability was significantly correlated with the domain-specific WM-PAD. In contrast, all behavioral measures of the conditions in the picture priming task were significantly associated with chronological age. The results suggest that chronological aging and WM aging have differential effects on language-related word retrieval functions, and support that cognitive alterations in word-finding functions involve not only the domain-specific processing within the frontotemporal language network but also the domain-general processing of executive functions in the fronto-parieto-occipital (or multi-demand) network. The findings further indicate that the phonological aspect of word retrieval ability declines as cerebral WM ages, whereas the semantic aspect is relatively resilient or unrelated to WM aging.

Distinct and shared cerebral activations in processing innocuous versus noxious contact heat revealed by functional magnetic resonance imaging.

Whether innocuous heat (IH)-exclusive brain regions exist and whether patterns of cerebral responses to IH and noxious heat (NH) stimulations are similar remain elusive. We hypothesized that distinct and shared cerebral networks were evoked by each type of stimulus. Twelve normal subjects participated in a functional MRI study with rapidly ramped IH (38 degrees C) and NH (44 degrees C) applied to the foot. Group activation maps demonstrated three patterns of cerebral activation: (1) IH-responsive only in the inferior parietal lobule (IPL); (2) NH-responsive only in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2), posterior insular cortex (IC), and premotor area (PMA); and (3) both IH- and NH-responsive in the middle frontal gyrus, inferior frontal gyrus (IFG), anterior IC, cerebellum, superior frontal gyrus, supplementary motor area, thalamus, anterior cingulate cortex (ACC), lentiform nucleus (LN), and midbrain. According to the temporal analysis of regions of interest, the IPL exclusively responded to IH, and the S2, posterior IC, and PMA were exclusively activated by NH throughout the entire period of stimulation. The IFG, thalamus, ACC, and LN responded differently during different phases of IH versus NH stimulation, and the NH-responsive-only S1 responded transiently during the early phase of IH stimulation. BOLD signals in bilateral IPLs were specifically correlated with the ratings of IH sensation, while responses in the contralateral S1 and S2 were correlated with pain intensity. These results suggest that distinct and shared spatial and temporal patterns of cerebral networks are responsible for the perception of IH and NH.

Cell therapy generates a favourable chemokine gradient for stem cell recruitment into the infarcted heart in rabbits.

AIMS: Stem cell recruitment into the heart is determined by a concentration gradient of stromal-derived factor 1 (SDF-1) from bone marrow to peripheral blood and from blood to injured myocardium. However, this gradient is decreased in chronic myocardial infarction (MI). This study evaluated the effect of cell therapy using bone marrow stromal cells (BMSCs) on an SDF-1 gradient in post-infarction rabbits. METHODS AND RESULTS: Myocardial infarction was induced in male New Zealand white rabbits (2.5-3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were randomized to either saline or BMSC (2 x 10(6) autologous BMSCs injected into the left ventricular cavity) treatment. Four weeks after therapy, the SDF-1 gradients from bone marrow to blood and from blood to myocardium increased in the BMSC group compared with the saline group. This was accompanied by an increase in cells positive for CD34, CD117, and STRO-1 in the myocardium, resulting in more capillary density, better cardiac function, and a decrease in infarct size. CONCLUSION: Generation of an SDF-1 gradient towards the heart is a novel effect of BMSC-based cell therapy. This effect facilitates stem cell recruitment into remodelled myocardium and supports improvement in cardiac function.

Perfusion of residual viable myocardium in nontransmural infarct zone after intervention: MR quantitative myocardial blood flow measurement.

PURPOSE: To assess regional myocardial perfusion in patients with chronic myocardial infarction (MI) in relationship to the extent of residual viable myocardium. MATERIALS AND METHODS: The study was approved by the local ethics committee; written informed consent was obtained from each participant. Twenty-nine patients with first onset of MI who underwent successful primary percutaneous coronary intervention at least 6 months thereafter were studied. Delayed enhancement magnetic resonance (MR) imaging was performed to define the infarct zone and its viable myocardial ratio (VMR), quantified by the percentage of the nonscarred pixels relative to the total pixels in the infarct zone. First-pass contrast material-enhanced MR imaging was performed to estimate regional perfusion and myocardial perfusion reserve (MPR) in the infarct region. Paired comparisons in perfusion and MPR were tested with nonparametric Wilcoxon matched-pairs test. A difference with P < .05 was considered significant. Correlation was tested with Pearson analysis. RESULTS: The infarct region showed significant impairment of regional perfusion at rest (mean, 0.966 [mL x min(-1)]/g +/- 0.271 [standard deviation] vs 1.151 [mL x min(-1)]/g +/- 0.282; P = .024) and during stress (mean, 1.789 [mL x min(-1)]/g +/- 0.732 vs 2.753 [mL x min(-1)]/g +/- 0.806; P < .0001) and a reduced MPR (mean, 1.923 +/- 0.678 vs 2.486 +/- 0.836; P < .0001) as compared with remote myocardium. The estimated perfusion, with stress, of the residual viable myocardium was preserved (2.993 [mL x min(-1)]/g +/- 1.451 vs 2.753 [mL x min(-1)]/g +/- 0.806), and the difference was not significant. Furthermore, stress perfusion (R = 0.385; P = .039) and MPR (R = 0.434; P = .018) in the infarct zone were significantly correlated with VMR, suggesting that preservation of myocardial perfusion in the infarct region reflects the amount of viable myocardium. CONCLUSION: Reduced perfusion in the infarct zone is related to the extent of the viable myocardium.

Interactive 3D hybrid PET/CT imaging in the identification of myocardial viability in patients after myocardial infarction: feasibility study and clinical implications.

BACKGROUND/PURPOSE: Clinical decision-making in coronary artery disease requires integrated information on myocardial viability and coronary arteries, and cross-modality registration could facilitate this process. The recent emergence of hybrid positron emission tomography (PET)/computed tomography (CT) allows acquisition of this information in one study session; however, clinically useful software capable of presenting three-dimensional (3D) fused images to assess the relationship between myocardium and coronary arteries is limited. METHODS: Patients with prior myocardial infarction were examined using electrocardiographically gated 18F-fluorodeoxyglucose PET and 16-slice CT. RESULTS: There were seven patients; mean age was 59 +/- 15 years and six were male. Using 3D reconstruction, coregistration and interactive display, the topographical relationship between myocardial viability and coronary arteries was clearly identified. CONCLUSION: We present a protocol to acquire CT coronary angiography and PET data and to visualize 3D fused images with an interactive visualization interface. This image coregistration is potentially useful to facilitate the process of image interpretation and decision-making.

Diffusion tensor magnetic resonance imaging mapping the fiber architecture remodeling in human myocardium after infarction: correlation with viability and wall motion.

BACKGROUND: Diffusion tensor magnetic resonance imaging (DT-MRI) provides a means for nondestructive characterization of myocardial architecture. We used DT-MRI to investigate changes in direction-dependent water diffusivity to reflect alterations in tissue integrity (trace apparent diffusion coefficients [ADCs] and fractional anisotropy [FA]), as well as indicators of remodeling of fiber helix angles, in patients after myocardial infarction. METHODS AND RESULTS: Thirty-seven patients (35 men, 2 women; median age, 59) after acute myocardial infarction (median interval from onset, 26 days) were enrolled. DT-MRI was performed at the midventricular level to measure trace ADC, FA, and helix angles of myofibers. Helix angles were grouped into left-handed helical fibers, circumferential fibers, and right-handed helical fibers. Measurements were correlated with viability and regional wall motion assessed by contrast-delay-enhancement and cine MRI, respectively. The infarct zone showed significantly increased trace ADC and decreased FA than the remote zone. The percentage of left-handed helical fibers increased from the remote zone (mean +/- SD, 13.3 +/- 5.8%) to the adjacent zone (19.2 +/- 9.7%) and infarct zone (25.8 +/- 18.4%) (MANOVA, P = 0.004). The percentage of right-handed helical fibers decreased from the remote zone (35.0 +/- 9.0%) to the adjacent zone (25.5 +/- 11.5%) and infarct zone (15.9 +/- 9.2%) (P < 0.001). Multiple linear regression showed that the percentage of left-handed helical fibers of the infarct zone was the strongest correlate of infarct size and predictor of ejection fraction. CONCLUSIONS: In vivo DT-MRI of postinfarct myocardium revealed a significant increase in trace ADC and a decrease in FA, indicating altered tissue integrity. The redistribution of fiber architecture correlated with infarct size and left ventricular function. This technique may help us understand structural correlates of functional remodeling after infarction.

Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1.

UNLABELLED: High tissue matrix metalloproteinase (MMP) activity has been associated with advanced atherosclerosis and plaque rupture. 18F-FDG uptake has been reported to detect inflammation. This investigation examined the vascular 18F-FDG uptake by PET/CT and its correlation with circulating MMP-1 levels. METHODS: We examined 25 consecutive patients with significant carotid stenosis and 22 healthy control subjects using 18F-FDG PET/CT. The leukocyte counts, C-reactive protein (CRP), and MMP-1 were measured. RESULTS: 18F-FDG arterial uptake, as well as calcifications, was significantly higher in extensive distributions in patients with established carotid stenosis. However, their distribution was not consistently overlapping. The values of circulating MMP-1 and leukocyte counts were significantly higher in patients with carotid stenosis (all P < 0.05). In addition, subjects with higher 18F-FDG uptake (maximum SUV > 2.0) in target lesions had higher baseline and poststenting MMP-1 levels (all P < 0.05). CONCLUSION: We provide a link between 18F-FDG uptake and circulating MMP-1. 18F-FDG PET/CT could be used as an adjunct to the clinical management of high-risk atherosclerosis and an in vivo tool to study plaque biology.