Early prediction of response to neoadjuvant chemotherapy in breast cancer patients: comparison of single-voxel (1)H-magnetic resonance spectroscopy and (18)F-fluorodeoxyglucose positron emission tomography.

OBJECTIVES: To prospectively compare performances of single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pathologic response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Thirty-five breast cancer patients who received NAC and subsequent surgery were prospectively enrolled. MRS and FDG-PET were performed before and after the 1st NAC cycle. Percentage changes of total choline-containing compounds (tCho) via MRS, and maximum and peak standardized uptake values (SUVmax, SUVpeak) and total lesion glycolysis (TLG) via FDG-PET were measured, and their performances in predicting pathologic complete response (pCR) were compared. RESULTS: Of the 35 patients, 6 showed pCR and 29 showed non-pCR. Mean % reductions of tCho, SUVmax, SUVpeak, and TLG of the pCR group were larger than those of the non-pCR group (-80.3 ± 13.9 % vs. -32.1 ± 49.4 %, P = 0.025; -54.7 ± 22.1 % vs. -26.3 ± 33.7 %, P = 0.058; -60.7 ± 18.3 % vs. -32.3 ± 23.3 %, P = 0.009; -89.5 ± 8.5 % vs. -52.6 ± 36.2 %, P = 0.020). Diagnostic accuracy (area under ROC curve; Az, 0.911) of the % reduction of tCho was comparable to those of %SUVmax (0.822), SUVpeak (0.862), and TLG (0.879) in distinguishing pCR from non-pCR (all P > 0.05). CONCLUSION: MRS showed comparable performance to FDG-PET in early prediction of pCR in breast cancer patients. KEY POINTS: • MRS can predict response to NAC in breast cancer post-1 (st) cycle. • Changes in tCho and SUV after NAC reflect tumour cellularity changes. • MRS can be an alternative to FDG-PET in predicting response to NAC.

COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder.

Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole-brain characterization of large-scale axonal connectivity differences in attention-deficit/hyperactivity disorder (ADHD) associated with catechol-O-methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val-homozygous (N = 29) compared with those who were Met-carriers (N = 29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8-week open-label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met-carriers compared to those who were Val-homozygous (P < 0.05, family-wise error-corrected). A measure of white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine-related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome.

Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder.

BACKGROUND: Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics. METHODS: Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls. RESULTS: We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders. LIMITATIONS: Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants. CONCLUSION: We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.

Extrastriatal dopaminergic changes in Parkinson's disease patients with impulse control disorders.

OBJECTIVE: To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD). METHOD: A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised manners. RESULTS: Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects. CONCLUSIONS: A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.

In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Endolymphatic hydrops asymmetry distinguishes patients with Meniere's disease from normal controls with high sensitivity and specificity.

Background: Many endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls. Methods: Gadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age-/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10-15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in µL) of the endolymphatic and perilymphatic spaces. Results: For the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls. Conclusion: Compared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Correlation of perfusion parameters on dynamic contrast-enhanced MRI with prognostic factors and subtypes of breast cancers.

PURPOSE: To investigate whether a correlation exists between perfusion parameters obtained from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and prognostic factors or immunohistochemical subtypes of breast cancers. MATERIALS AND METHODS: Quantitative parameters (K(trans) , k(ep) , and v(e) ) of 70 invasive ductal carcinomas were obtained using DCE-MRI as a postprocessing procedure. Correlations between parameters and prognostic factors, including tumor size, axillary nodal status, histologic grade, nuclear grade, expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, bcl-2, and human epidermal growth factor receptor 2 (HER2) and subtypes categorized as luminal (ER or PR-positive), triple negative (ER or PR-negative, HER2-negative), and HER2 (ER and PR-negative, HER2 overexpression) were analyzed. RESULTS: Mean K(trans) was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.007), with a high nuclear grade than with a low nuclear grade (P = 0.002), and with ER negativity than ER positivity (P = 0.056). Mean k(ep) was higher in tumors with a high histologic grade than with a low histologic grade (P = 0.005), with a high nuclear grade than with a low nuclear grade (P = 0.001), and with ER negativity than with ER positivity (P = 0.043). Mean v(e) was lower in tumors with a high histologic grade than with a low histologic grade (P = 0.038) and with ER negativity than with ER positivity (P = 0.015). Triple-negative cancers showed a higher mean k(ep) than the luminal type (P = 0.015). CONCLUSION: Breast cancers with higher K(trans) and k(ep) , or lower v(e) , had poor prognostic factors and were often of the triple-negative subtype.

Three-Dimensional Volumetric Measurement of Endolymphatic Hydrops in Meniere's Disease.

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages. Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods. Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear. Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.

Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery.

Highly versatile nanocomposite nanoparticles were synthesized by decorating the surface of mesoporous dye-doped silica nanoparticles with multiple magnetite nanocrystals. The superparamagnetic property of the magnetite nanocrystals enabled the nanoparticles to be used as a contrast agent in magnetic resonance (MR) imaging, and the dye molecule in the silica framework imparted optical imaging modality. Integrating a multitude of magnetite nanocrystals on the silica surface resulted in remarkable enhancement of MR signal due to the synergistic magnetism. An anticancer drug, doxorubicin (DOX), could be loaded in the pores and induced efficient cell death. In vivo passive targeting and accumulation of the nanoparticles at the tumor sites was confirmed by both T2 MR and fluorescence imaging. Furthermore, apoptotic morphology was clearly detected in tumor tissues of mice treated with DOX loaded nanocomposite nanoparticles, demonstrating that DOX was successfully delivered to the tumor sites and its anticancer activity was retained.

Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer.

PURPOSE: To evaluate the potential of diffusion-weighted (DW) magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map in the prediction of response to neoadjuvant chemotherapy in patients with breast cancer. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, which waived the informed consent requirement. Fifty-three consecutive women (mean age, 43.7 years; median age, 42.0 years; age range, 24-65 years) with 53 invasive breast cancers (mean diameter, 5.0 cm; median diameter, 4.2 cm; diameter range, 2.0-13.3 cm) who had undergone chemotherapy were included. Both DW MR imaging (b values, 0 and 750 sec/mm(2)) and dynamic contrast material-enhanced (DCE) MR imaging were performed at 1.5 T before and after chemotherapy prior to surgery. Mean time from initiation of chemotherapy to posttreatment ADC measurement was 54 days (range, 48-62 days). Average ADC for three regions of interest per tumor on ADC maps was calculated. Patients with a reduction in tumor diameter of at least 30% after chemotherapy at DCE MR imaging were defined as responders. Pretreatment ADCs and percentage increases in ADC after chemotherapy in responders and nonresponders were compared. The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was calculated with receiver operating characteristic curve analysis. RESULTS: After chemotherapy, 36 (68%) patients were classified as responders, and 17 (32%) were classified as nonresponders. Pretreatment mean ADC ([1.036 ± 0.015] × 10(-3) mm(2)/sec [standard error]) of responders was significantly lower than that of nonresponders ([1.299 ± 0.079] × 10(-3) mm(2)/sec) (P = .004). Furthermore, mean percentage ADC increase of responders (47.9% ± 4.8) was higher than that of nonresponders (18.1% ± 4.5) (P < .001). The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was 1.17 × 10(-3) mm(2)/sec, which yielded a sensitivity of 94% (95% confidence interval [CI]: 81%, 99%) and a specificity of 71% (95% CI: 44%, 90%). CONCLUSION: Patients with breast cancer and a low pretreatment ADC tended to respond better to chemotherapy. Prediction of response to neoadjuvant chemotherapy with DW MR imaging might help physicians individualize treatments and avoid ineffective chemotherapy.

Smart magnetic fluorescent nanoparticle imaging probes to monitor microRNAs.

An imaging system that can be used to evaluate the expression levels of microRNAs during neuronal development can provide noninvasive information for investigating a variety of biological phenomena related to microRNAs (miRNAs, miRs). Herein, the development of a novel imaging platform to monitor intracellular miR124a during neuronal differentiation is reported using rhodamine-coated cobalt ferrite magnetic fluorescent (MF) nanoparticles linked to a quenching molecular system containing an miR124a binding sequence (MF-miR124a beacon). During neuronal differentiation, in vitro fluorescence signals of the MF-miR124a beacon are significantly increased under conditions where miR124a is highly expressed, and dramatically return to the original quenched fluorescence after anti-miR124a treatment. In vivo fluorescence images show enhanced fluorescence signals in mice with P19 cells within a poly-L-lactic acid scaffold after induction of neuronal differentiation. In addition, magnetic resonance (MR) images provide in vivo tracking of cells containing the MF-miR124a beacon. These studies represent the first step toward the use of nanotechnological imaging of mature miRNA, and this technique could be used for cellular tracking with a MR imaging system as well as for simultaneous monitoring of the miRNA expression pattern in vivo.

Tumor targeting chitosan nanoparticles for dual-modality optical/MR cancer imaging.

We report tumor targeting nanoparticles for optical/MR dual imaging based on self-assembled glycol chitosan to be a potential multimodal imaging probe. To develop an optical/MR dual imaging probe, biocompatible and water-soluble glycol chitosan (M(w) = 50 kDa) were chemically modified with 5beta-cholanic acid (CA), resulting in amphiphilic glycol chitosan-5beta-cholanic acid conjugates (GC-CA). For optical imaging near-infrared fluorescence (NIRF) dye, Cy5.5, was conjugated to GC-CA resulting in Cy5-labeled GC-CA conjugates (Cy5.5-GC-CA). Moreover, in order to chelate gadolinium (Gd(III)) in the Cy5.5-GC-CA conjugates, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was directly conjugated in Cy5.5-GC-CA. Finally, the excess GdCl(3) was added to DOTA modified Cy5.5-GC-CA conjugates in distilled water (pH 5.5). The freshly prepared Gd(III) encapsulated Cy5.5-GC-CA conjugates were spontaneously self-assembled into stable Cy5.5 labeled and Gd(III) encapsulated chitosan nanoparticles (Cy5.5-CNP-Gd(III)). The Cy5.5-CNP-Gd(III) was spherical in shape and approximately 350 nm in size. From the cellular experiment, it was demonstrated that Cy5.5-CNP-Gd(III) were efficiently taken up and distributed in cytoplasm (NIRF filter; red). When the Cy5.5-GC-Gd(III) were systemically administrated into the tail vein of tumor-bearing mice, large amounts of nanoparticles were successfully localized within the tumor, which was confirmed by noninvasive near-infrared fluorescence and MR imaging system simultaneously. These results revealed that the dual-modal imaging probe of Cy5.5-CNP-Gd(III) has the potential to be used as an optical/MR dual imaging agent for cancer treatment.

The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells.

This study was undertaken to compare the labeling efficiencies of three iron-oxide based MRI contrast agents [Feridex, Resovist and monocrystalline iron oxide (MION)] and to evaluate their effects on the biological properties of human mesenchymal stem cells (hMSCs). The hMSCs were cultivated for 1 and 7 days after 24-h labeling with iron oxide nanoparticles (12.5 microg Fe/mL) in the presence of poly-L-lysine (0.75 microg/mL). The hMSCs were labeled more efficiently with use of Feridex, Resovist as compared to MION. No significant differences were observed in terms of viability and proliferation of labeled hMSCs. The level of Oct-4 mRNA increased in labeled hMSCs at day 1 and the cellular phenotype changed from CD45-/CD44+/CD29+ to CD45low/CD44+/CD29+ at day 7, which closely resembles the phenotype of fresh bone marrow-derived hMSCs. Our study has demonstrated that the Feridex or Resovist is the preferred labeling agent for hMSCs. There was a change in Oct-4 and CD45 expression after labeling.

Childhood moyamoya disease: quantitative evaluation of perfusion MR imaging--correlation with clinical outcome after revascularization surgery.

PURPOSE: To evaluate whether perfusion magnetic resonance (MR) imaging can depict hemodynamic status after revascularization surgery and whether changes at perfusion MR imaging after revascularization surgery correspond with clinical outcome in moyamoya disease. MATERIALS AND METHODS: An institutional review board approved this retrospective study; informed consent was waived. Pre- and postoperative perfusion MR imaging data in 67 children with moyamoya disease (mean age, 7.2 years; range, 2-13 years) were included. Regional time to peak (rTTP) and regional cerebral blood volume (rCBV) were calculated by adjusting cerebral time to peak (TTP) and cerebral blood volume (CBV) values by using cerebellar reference values. For quantitative regional analysis, pixel values were divided into five categories (>0, >2, >4, >6, and >8 seconds), and percentages of pixels in rTTP meeting these time conditions were calculated. Changes in the values after revascularization were calculated. Postoperative clinical outcomes were categorized as follows: 1 indicated excellent; 2, good; 3, fair; and 4, poor. Pre- and postoperative perfusion parameters were compared by using a paired t test; relationships between perfusion parameters and clinical outcomes were investigated by using one-way analysis of variance, with a significance level of .05. RESULTS: rTTP, rCBV, and percentage of pixels of rTTP decreased significantly after revascularization surgery. Pre- and postoperative rTTP were significantly different for the clinical outcome categories. Change in rTTP and change in percentage of pixels of rTTP (>0 seconds to >6 seconds) were significantly different for the clinical outcome categories. CONCLUSION: TTP and CBV perfusion maps can depict hemodynamic status after revascularization surgery in moyamoya disease. Furthermore, changes in TTP perfusion maps after revascularization surgery correspond with clinical outcome in patients with moyamoya disease.

Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles.

This study was undertaken to investigate the in vitro effect of islet labeling with iron oxide nanoparticles for MRI on islet viability, insulin secretion, and gene expression. Isolated rat islets were labeled with Resovist (25-200 microg Fe/mL, a clinically approved MRI contrast agent) in the presence or absence of poly-l-Lysine (PLL, 1.5 microg/mL) for 48 h. The iron content of labeled islets was found to increase in a dose-dependent manner. More than 90% of the islets were labeled with 100 microg Fe/mL. We confirmed the localizations of iron oxide nanoparticles within islet beta-cells by insulin immunostaining. As the concentration of Resovist increased, T(2) values as determined by T(2)-weighted MRI on a 1.5 Tesla MR scanner decreased. Labeling of 100 islets in a medium containing 100 microg Fe/mL of Resovist in the absence of PLL provided sufficient contrast for islet visualization on T(2)-weighted MRI. MTT assays showed that the viability of labeled islets was not different from that of unlabeled islets. No statistical difference was observed between labeled (2.91 +/- 0.36) and unlabeled islets (2.83 +/- 0.61) in terms of the ability to secrete insulin, as determined by the glucose stimulation index. We also evaluated the effect of iron oxide incorporation on the gene expressions in islet cells using RT-PCR (reverse transcriptase PCR). Insulin expression in labeled islets was significantly elevated (1.83 +/- 0.25 fold vs. unlabeled; p = 0.005), but not the expression of somatostatin (1.39 +/- 0.18 fold vs. unlabeled; p = 0.085) or glucagons (1.28 +/- 0.13 fold vs. unlabeled; p = 0.09). Expression of an important transcription factor for insulin gene transcription, BETA2 (beta-cell E-box trans-activator), was increased in labeled islets (1.67 +/- 0.15 fold vs. unlabeled; p = 0.029). The findings of this study indicate that Resovist provides a satisfactory means to image islets and has no deleterious effect on islet function or gene expression.

Simple and generalized synthesis of oxide-metal heterostructured nanoparticles and their applications in multimodal biomedical probes.

Heterostructured nanoparticles composed of metals and Fe3O4 or MnO were synthesized by thermal decomposition of mixtures of metal-oleate complexes (for the oxide component) and metal-oleylamine complexes (for the metal component). The products included flowerlike-shaped nanoparticles of Pt-Fe3O4 and Ni-Fe3O4 and snowmanlike-shaped nanoparticles of Ag-MnO and Au-MnO. Powder X-ray diffraction patterns showed that these nanoparticles were composed of face-centered cubic (fcc)-structured Fe3O4 or MnO and fcc-structured metals. The relaxivity values of the Au-MnO and Au-Fe3O4 nanoparticles were similar to those of the MnO and Fe3O4 nanoparticles, respectively. Au-Fe3O4 heterostructured nanoparticles conjugated with two kinds of 12-base oligonucleotide sequences were able to sense a complementary 24-mer sequence, causing nanoparticle aggregation. This hybridization-mediated aggregation was detected by the overall size increase indicated by dynamic light scattering data, the red shift of the surface plasmon band of the Au component, and the enhancement of the signal intensity of the Fe3O4 component in T2-weighted magnetic resonance imaging.

Objects and their icons in the brain: the neural correlates of visual concept formation.

We are constantly exposed to symbols such as traffic signs, emoticons in internet communication, or other abstract representations of objects as well as, of course, the written words. However, aside from the word reading, little is known about the way our brain responds when we read non-lexical iconic symbols. By using functional MRI, we found that the watching of icons recruited manifold brain areas including frontal and parietal cortices in addition to the temporo-occipital junction in the ventral pathway. Remarkably, the brain response for icons was contrasted with the response for corresponding concrete objects with the pattern of 'hyper-cortical and hypo-subcortical' brain activation. This neural underpinning might be called the neural correlates for visual concept formation.

Diffusion-weighted MR: therapeutic evaluation after chemoembolization of VX-2 carcinoma implanted in rabbit liver.

RATIONALE AND OBJECTIVES: The study goal was to evaluate the ability of diffusion-weighted imaging (DWI) in assessing the viability of rabbit liver VX-2 tumor after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: VX-2 tumors were grown in the livers of 19 rabbits, and chemoembolization was performed. MR imaging was acquired 1 week after TACE. The rabbits were killed for histologic investigation immediately after MR imaging, and the proportion of viable tumor was calculated based on histopathologic examination. Apparent diffusion coefficient (ADC) values were measured in viable and necrotic tumor portion, and were compared using the paired Student's t test. RESULTS: Viable tumors were absent (n = 3), less than 5% (n = 6), and 5% or more (n = 10) at pathology examination. On DWI, three tumors with no viable portion were interpreted as having no viable portion, but three of six tumors with a viable portion of less than 5% were considered as having no viable portion. The mean ADC values of necrotic and viable tumor were 1.653 +/- 0.126 mm(2)/sec and 0.883 +/- 0.407 mm(2)/sec (b = 1000 sec/mm(2)), respectively, and the ADC values of necrotic tumors were significantly greater than those in viable tumors (p < .01). CONCLUSION: Although DWI is a useful tool for assessing tumor viability, viable tumor may not be detected on DWI when it is too small.

Evolution of VX2 carcinoma in rabbit tibia: magnetic resonance imaging with pathologic correlation.

OBJECTIVE: To evaluate the evolution of a metastatic bone tumor model with MRI-pathology correlation. MATERIALS AND METHODS: VX2 carcinoma was implanted into the tibiae of 20 rabbits. The rabbits were divided into four groups of five (Groups I-IV). MRI was repeated at 1-week interval up to the fourth week, including sagittal T1-weighted image (T1WI), T2-weighted image (T2WI), gadolinium-enhanced fat-suppressed T1WI (GdT1WI), and diffusion-weighted image (DWI). Each group was sacrificed after the imaging, then histological examination for the tibiae with an implanted tumor was performed and MRI-pathologic correlation was done. RESULTS: On MRI-pathology correlation, the corresponding findings were as follows; low SI on T1WI, T2WI-tumor cells, fibrosis (1 week); central low SI on T1WI, T2WI, GdT1WI -tumor cells with fibrosis and necrosis; peripheral high SI on T2WI, DWI, GdT1WI-edema, fibrosis (2 weeks); heterogeneous SI with central low SI on T2WI, DWI-tumor cell nests with extensive necrosis, fibrosis; high SI on T2WI along periosteum-periosteal reaction; high SI around low SI and in bone marrow on T2WI, DWI, GdT1WI-edema, fibrosis; low SI on T1WI in surrounding bone marrow-tumor extension (3-4 weeks). CONCLUSION: The evolution of VX2 carcinoma model was well depicted on MR imaging. Necrosis and extent of tumor were best depicted on enhanced, fat-suppressed T1-weighted images. Heterogeneity of the tumor, peripheral edema, and fibrosis were represented well on T2-weighted images. Diffusion-weighted imaging could have a role in depicting necrosis in the evaluation of bone tumor.

Use of diffusion tensor imaging to evaluate weakness.

OBJECT: Recently, diffusion tensor (DT) imaging was introduced to demonstrate white matter tracts. However, research interest has focused on the anatomical rather than the functional aspects of this imaging modality. The authors undertook a functional analysis of DT imaging to determine the relationship between weakness and changes on DT images. METHODS: Diffusion tensor images were obtained in 23 patients with lesions located adjacent to the pyramidal tract. Patients were classified according to their motor deficit. Axial magnetic resonance image sections through the maximum tumor diameters were selected and the mean apparent diffusion coefficients (ADCs) and mean fractional anisotropies (FAs) were measured. One ovoid region of interest (ovROI) was placed in the center of the pyramidal tract and another was designed to include the whole pyramidal tract at the same axial level (wROI). To determine intraobserver variability, a single neurosurgeon measured mean ADCs and FAs four times by using these two different ROI types without knowledge of any clinical information. To determine interobserver variability, a second neurosurgeon who was also unaware of any clinical information measured the mean ADCs and FAs by using the wROI method. The five measurements produced the same results. The mean FA at the lesion side of the pyramidal tract was significantly lower in patients with weakness (p < 0.01). Little intraobserver measurement variability occurred using the ovROI method, and no interobserver variability occurred using the wROI method. CONCLUSIONS: Motor weakness was significantly related to a low mean FA in the pyramidal tract on the lesion side. Designing an ROI that includes the whole pyramidal tract is an easier and more reproducible method than using an ovROI method.