T2-weighed Magnetic Resonance Imaging Research Articles

Inclination of the small laminar slope angle leads to lumbar spinal stenosis due to hypertrophy of the ligamentum flavum.

This study was designed to investigate the relationship between the laminar slope angle (LSA) and the lumbar disc degenerative grade, the cross-section area (CSA) of multifidus muscle, the muscle-fat index, and the thickness of the ligamentum flavum. Retrospective analysis of 122 patients who were scheduled to undergo a lumbar operation for diagnoses associated with degenerative lumbar disease between January and December 2017. The L4-L5 disc grade was evaluated from preoperative sagittal T2-weighed magnetic resonance imaging of the lumber region; the CSA of the multifidus and muscle-fat index were measured at the L4 level, while the thickness of the ligamentum flavum was measured at the L4-L5 facet level from axis T2-weighed magnetic resonance imaging. The slope of the laminar was evaluated from preoperative three-dimensional computer tomography at the tip level of the facet joints and selected by the axis plane. Independent-sample T-tests were used to assess the association between age and measurement indices. Our results showed that age was positively connected with the LSA of L4 and L5 in different patients, although there was no significant difference between age and the difference of the two segment LSA. Partial correlation analysis, excluding the interference of age, revealed a strong negative relationship between the LSA of L4 and the thickness of the ligamentum flavum, irrespective of whether we considered the left or right. However, there was no correlation with lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. The thickness of the ligamentum flavum showed changes with anatomical differences in the LSA, but not the lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. A small change in LSA may cause large mechanical stress; this may be one of the causative factors responsible for lumbar spinal stenosis.

Radiomics With Ensemble Machine Learning Predicts Dopamine Agonist Response in Patients With Prolactinoma.

Early identification of the response of prolactinoma patients to dopamine agonists (DA) is crucial in treatment planning. To develop a radiomics model using an ensemble machine learning classifier with conventional magnetic resonance images (MRIs) to predict the DA response in prolactinoma patients. Retrospective study. Severance Hospital, Seoul, Korea. A total of 177 prolactinoma patients who underwent baseline MRI (109 DA responders and 68 DA nonresponders) were allocated to the training (n = 141) and test (n = 36) sets. Radiomic features (n = 107) were extracted from coronal T2-weighed MRIs. After feature selection, single models (random forest, light gradient boosting machine, extra-trees, quadratic discrimination analysis, and linear discrimination analysis) with oversampling methods were trained to predict the DA response. A soft voting ensemble classifier was used to achieve the final performance. The performance of the classifier was validated in the test set. The ensemble classifier showed an area under the curve (AUC) of 0.81 [95% confidence interval (CI), 0.74-0.87] in the training set. In the test set, the ensemble classifier showed an AUC, accuracy, sensitivity, and specificity of 0.81 (95% CI, 0.67-0.96), 77.8%, 78.6%, and 77.3%, respectively. The ensemble classifier achieved the highest performance among all the individual models in the test set. Radiomic features may be useful biomarkers to predict the DA response in prolactinoma patients.

Quantitative Assessment of Bone Marrow Edema in Adolescent Athletes with Lumbar Spondylolysis Using Contrast Ratio on Magnetic Resonance Imaging.

Study DesignProspective cohort study.PurposeTo quantitatively evaluate bone marrow edema (BME) in the pedicle on magnetic resonance imaging (MRI) for adolescent athlete patients with spondylolysis.Overview of LiteratureSpondylolysis, a stress fracture of the pars interarticularis, is a common occurrence in adolescent athletes with low back pain. T2-weighed fat-saturated MRI is reportedly useful for the detection of BME in the pedicle in the early stage of spondylolysis; however, to our knowledge, the quantitative assessment of BME in spondylolysis has not been reported.MethodsAdolescent athletes with spondylolysis, including those with symptoms of low back pain, were enrolled. The sporting activity of the patients was restricted, and a hard brace was attached to the spine. The BME range of interest was taken on T2-weighed fat-saturated MRI, and the signal intensity (SI) of the BME (SIedema) was measured. The contrast ratio (CR) between the SI of the BME and SI of the spinal cord (SIcord) was calculated per the following formulae: CRedema=(SIedema−SIcord)/(SIedema+SIcord). The CR of the normal pedicle was measured as a control per the following formulae: CRcontrol=(SIcontrol−SIcord)/(SIcontrol+SIcord).ResultsThe study enrolled 32 men and one woman; the mean patient age was 15.2 years (range, 12–18 years). The average CR of the edema and normal pedicle at the first visit was 0.506 (range, 0.097–0.804) and 0.137 (range, −0.741 to 0.572), respectively. The CR of the edema was significantly higher as compared to that of the normal pedicle (p<0.01). MRI that was performed 1 month after the first visit showed that the CR of the edema had decreased to 0.204 (range, −0.152 to 0.517). The CR of the edema 1 month thereafter was significantly lower than that at the first visit (p<0.01).ConclusionsQuantitative assessment of BME using CR on MRI is useful in the evaluation of the healing process of spondylolysis.

Analysis of the Correlation Between Cerebrospinal Fluid Space and Outcomes of Anterior Controllable Antedisplacement and Fusion for Cervical Myelopathy Due to Ossification of the Posterior Longitudinal Ligament

We investigated whether the cerebrospinal fluid (CSF) space on magnetic resonance imaging (MRI) correlates with the outcomes of anterior controllable antedisplacement and fusion (ACAF) for ossification of the posterior longitudinal ligament (OPLL). A total of 53 patients with OPLL who had undergone ACAF were enrolled. The Japanese Orthopaedic Association (JOA) scale, visual analog scale, and neck disability index were used to evaluate the clinical outcomes. The area of CSF space and spinal cord on T2-weighted MRI, the occupying rate of the CSF space and spinal cord, and the postoperative MRI score of the CSF space were measured. The patients were divided into 2 groups according to the JOA score improvement rate (IR). The relationship between the postoperative MRI score and the JOA score IR was analyzed. The patients in group A experienced better recovery compared with those in group B regarding the JOA, visual analog scale, and neck disability index score at the final follow-up visit. On both axial and sagittal T2-weighed MRI, patients in group A experienced lower improvement of the area of the spinal cord than in group B (P > 0.05). However, the mean improvement in the CSF space in group A was better than that in group B (62.86 ± 30.05 mm2 vs.-6.36 ± 24.58 mm2; P < 0.05), with a greater occupying rate of CSF space in group A at the final visit. A strong correlation was noted between the JOA score IR and postoperative CSF space score (P < 0.01). These results suggest that ACAF could provide good decompression of the spinal cord and neurological improvement. Also, recovery of the CSF space correlated closely with the surgical ACAF outcomes for cervical myelopathy due to OPLL.

Micellar Iron Oxide Nanoparticles Coated with Anti-Tumor Glycosides.

The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.

Improving sensitivity of magnetic resonance imaging by using a dual-targeted magnetic iron oxide nanoprobe

Developing an ultrasensitive and high-efficient molecular imaging probe for detection of malignant tumors is extremely needed in clinical and remains a big challenge. Here, we report a novel bispecific nanoprobe for dual-targeted T2-weighed magnetic resonance imaging (MRI) of COLO-205 colorectal cancer in vivo. First, the magnetic iron oxide nanoparticles (Fe3O4@OA) were synthesized by a thermal decomposition method. Then, PEGylation of the hydrophobic Fe3O4@OA was implemented by amphiphilic DSPE-PEG2000-COOH, producing water-soluble nanoparticles (Fe3O4@PEG). Lastly, arginine-glycine-asparticacid-tumornecrosis factor-related apoptosis-inducing ligand (RGD-TRAIL), a bispecific fusion protein, was conjugated with the nanoparticle to construct molecularly multi-targeted nanoprobe, which was defined as Fe3O4@RGD-TRAIL. This Fe3O4@RGD-TRAIL was proven to exhibit extremely high relaxation property (r2=534mM−1s−1) and saturation magnetization value (Ms=92 emu/g Fe). In vitro studies showed its dual-targeting combination capacity, favorable biocompatibility and strong ability to resist against the non-specific phagocytosis. Owing to these excellent advantages, high sensitive and efficient imaging of tumor was achieved in vivo. Therefore, this RGD-TRAIL conjugated nanoprobe could be developed as a multi-targeted contrast enhancement agent for magnetic resonance molecular imaging in detection of cancer.

In vitro Study of SPIONs-C595 as Molecular Imaging Probe for Specific Breast Cancer (MCF-7) Cells Detection

Background:Magnetic resonance imaging (MRI) plays an essential role in molecular imaging by delivering the contrast agent into targeted cancer cells. The aim of this study was to evaluate the C595 monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-C595) for the detection of breast cancer cell (MCF-7).Methods:The conjugation of monoclonal antibody and nanoparticles was confirmed using X-ray diffraction, transmission electron microscopy, and photon correlation spectroscopy. The selectivity of the nanoprobe for breast cancer cells (MCF-7) was obtained by Prussian blue, atomic emission spectroscopy, and MRI relaxometry.Results:The in vitro MRI showed that T2 relaxation time will be reduced 76% when using T2-weighed magnetic resonance images compared to the control group (untreated cells) at the dose of 200 μg Fe/ml, as the optimum dose. In addition, the results showed the high uptake of nanoprobe into MCF-7 cancer cells.Conclusion:The SPIONs-C595 nanoprobe has potential for the detection of specific breast cancer.

Estimation of the depth of the thoracic epidural space in children using magnetic resonance imaging.

BackgroundThe estimation of the distance from the skin to the thoracic epidural space or skin to epidural depth (SED) may increase the success rate and decrease the incidence of complications during placement of a thoracic epidural catheter. Magnetic resonance imaging (MRI) is the most comprehensive imaging modality of the spine, allowing for the accurate determination of tissue spaces and distances. The present study uses MRI-derived measurements to measure the SED and define the ratio between the straight and inclined SEDs at two thoracic levels (T6–7 and T9–10) in children.MethodsThe T2-weighed sagittal MRI images of 109 children, ranging in age from 1 month to 8 years, undergoing radiological evaluation unrelated to spine pathology were assessed. The SEDs (inclined and straight) were determined, and a comparison between the SEDs at two thoracic levels (T6–7 and T9–10) was made. Univariate and multivariate linear regression models were used to assess the relationship of the inclined thoracic T6–7 and T9–10 SED measurements with age, height, and weight.ResultsBody weight demonstrated a stronger association with the SED than did the age or height with R2 values of 0.6 for T6–7 and 0.5 for T9–10. The formulae describing the relationship between the weight and the inclined SED were T6–7 inclined (mm) = 7 + 0.9 × kg and T9–10 inclined (mm) = 7 + 0.8 × kg.ConclusionThe depth of the pediatric thoracic epidural space shows a stronger correlation with weight than with age or height. Based on the MRI data, the predictive weight-based formulas can serve as guide to clinicians for placement of thoracic epidural catheters.

White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort.

Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.

Correlation of magnetic resonance diffusion tensor imaging and clinical findings of cervical myelopathy

Background contextDespite significant advances in the development of diagnostic technology, the diagnosis of cervical myelopathy (CM) still remains based on the clinical findings, which do not provide the means for a sufficiently accurate diagnosis. Furthermore, conventional magnetic resonance imaging (MRI) using T1- and T2-weighted sequences lacks sensitivity to detect and characterize spinal cord lesions. Considering these uncertainties, several investigators have assessed the diagnostic value of diffusion tensor imaging (DTI), an advanced MRI technique that measures the diffusion of water molecules. PurposeTo determine the diagnostic value of DTI in CM in reliably characterizing spinal lesions and in associating them with the clinical findings. Study design/settingProspective cohort study. Patient sampleFifteen CM patients and five healthy volunteers without a history of neurological disorders or of symptoms as controls. Outcome measuresSymptoms and signs of CM were evaluated by the use of a modified Japanese Orthopedic Score and the other clinical findings. T2-weighed MRI was used to note the number of compressed levels. Diffusion tensor imaging results were measured according to two parameters, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), at anterior, lateral, and posterior regions of interest (ROIs) in each of five cervical vertebrae, C3–C7. MethodsOn diagnosis of CM by clinical evaluation and findings from T2-weighted MRI, the 15 subjects were assigned to two subgroups based on complaints, symptoms, and signs. The nine subjects who had typical CM symptoms such as motor weakness, gait disturbance, clumsiness of the hands, and unilateral hypesthesia were assigned to the paralysis subgroup. The other six subjects, whose main symptom was pain and who had vague signs of upper motor neuron injury despite a definitive finding of CM by T2-weighted MRI, were assigned to the pain subgroup. Once assignments had been made, subjects underwent DTI done by the use of the same scanner as for T2-weighted MRI. Results of DTI for each subgroup and controls were averaged, and the mean was used for comparisons. Diffusion tensor imaging results from the paralysis subgroup were sorted into affected and unaffected sides according to the presence or the absence of symptoms. ResultsThe paralysis subgroup and the pain subgroup had similar findings from T2-weighted MRI on presentation. The paralysis subgroup had statistically significantly decreased FA values in the anterior and lateral ROIs on the affected side and in the anterior ROIs on the unaffected side, compared with controls. The paralysis subgroup also had statistically significantly increased ADC values in the anterior ROIs of the affected side, compared with controls. The pain subgroup showed significantly increased ADC values in anterior, lateral, and posterior ROIs. ConclusionsUse of DTI to quantitatively compare compression in the cervical spinal cords of CM subjects and healthy controls explained individual differences in the clinical findings in the subjects. These findings even applied to CM subjects whose compressed spinal cords looked similar on conventional T2-weighted MRI. Therefore, DTI provided more accurate and reliable information than did conventional T2-weighted MRI about the relationship between spinal cord structure and clinical presentation of CM. Based on our DTI findings, we hypothesized that different clinical findings in CM are attributable to the stage of progression and the severity of pathologic change at presentation. We anticipate that the use of DTI to quantify the extent of myelopathological changes in CM could be more reliable than any other existing diagnostic tools and might provide invaluable information about selecting the optimal treatment for CM and predicting surgical outcomes and prognosis.

Collagen Unfolding Determines Fluid Transfer in the Interstitial Matrix

Local unfolding of collagen at physiologic temperatures is thought to facilitate interactions with enzymes and scaffold molecules during inflammation, tissue remodeling, and wound healing. Previous data showing high interstitial hydration potential (HP) in human and porcine dermis after collagen thermal unfolding and fibroblast death suggest that it also plays a role in local modulation of interstitial flows. To test this hypothesis, collagen was progressively unfolded in situ, and changes in HP and water influx-rate within the matrix were measured as a function of the extent of unfolding, which was quantified by differential scanning calorimetry in full-thickness dermal samples after timed heat-treatment at 60°C and equilibration at 4°C. HP was determined by osmotic stress techniques, and influx-rates from time-dependent gravimetric changes under 35mmHg osmotic counterpressure. Both increased linearly with the proportion of unfolded collagen: the HP by 1.08 ± 0.16 mmHg, and the influx-rate by 3.19 ± 0.39 μl/min /100g per each 1% of collagen unfolded (R2= 0.93 and 0. 95, respectively). The relative humidity and intensity of T2-weighed magnetic resonance images of the dermis also increased with the extent of collagen unfolding, confirming interfacial energy contributions to the HP - as predicted by the Kelvin relationship - and the expected hydrophobic nature of the newly formed protein/water interfaces, respectively. These results are fully consistent with the hypothesis and point to yet another potentially important function of local collagen unfolding in tissue homeostasis. As a plausible mechanism for HP and influx-rate increases with collagen unfolding, we propose that the surface tension of vapor/water interfaces under exposed hydrophobic clusters is higher than at hydrophilic interfaces; at nanometer scales, these differences generate local surface-tension gradients in the matrix that accelerate water influx and shift the HP.

Use of Patient-specific MRI-based Prostate Mold for Validation of Multiparametric MRI in Localization of Prostate Cancer

To demonstrate the use of a patient-specific magnetic resonance imaging (MRI)-based prostate mold to generate histologic sections that directly correlate to axial MRI slices in a patient with anteriorly located prostate cancer. Anteriorly located prostate cancer has traditionally been difficult to detect on digital rectal examination and transrectal ultrasound-guided biopsy. Multiparametric MRI has potential as a valuable tool for the diagnosis and focal treatment of prostate cancer. A significant difficulty to date has been accurate correlation between the magnetic resonance images and histopathologic specimens. A patient-specific mold from a preoperative T2-weighted MRI scan was created to hold and shape the prostate specimen. Slots for slicing were positioned at 6-mm increments coplanar to the axial MRI slices. After surgical excision, the specimen was inked to maintain the orientation and fixed in formalin. The seminal vesicles were excised, and the prostate was oriented in the mold such that the color-coding matched the anatomic labels on the mold. The specimen was sliced with a single blade and the resultant 6-mm tissue blocks were used for histologic analysis. Preoperative multiparametric MRI revealed a lesion in the right anterior transition zone that was positive on T2-weighed MRI, apparent diffusion coefficient maps of diffusion-weighted MRI, magnetic resonance spectroscopy, and dynamic contrast-enhanced MRI. The histologic sections obtained using the mold demonstrated a similar Gleason score 6 (3+3) lesion in the right anterior transition zone, correlating with the MRI findings. The use of patient-specific prostate molds to register the MRI findings with the histopathologic specimen in prostate cancer could offer several benefits compared with current specimen processing techniques. This technique might further validate MRI as an accurate tool for prostate cancer localization and staging.

The local pathology of interstitial edema: Surface tension increases hydration potential in heat-damaged skin

The local pathogenesis of interstitial edema in burns is incompletely understood. This ex vivo study investigates the forces mediating water-transfer in and out of heat-denatured interstitial matrix. Experimentally, full-thickness dermal samples are heated progressively to disrupt glycosaminoglycans, kill cells, and denature collagen under conditions that prevent water loss/gain; subsequently, a battery of complementary techniques including among others, high-resolution magnetic resonance imaging, equilibrium vapor pressure and osmotic stress are used to compare water-potential parameters of nonheated and heated dermis. The hydration potential (HP) determined by osmotic stress is a measure of the total water-potential defined empirically as the pressure at which no net water influx/efflux into/from the dermis is detected. Results show that after heat denaturation, the HP, the intensity of T2-weighed magnetic resonance images, and the vapor pressure increase indicating higher water activity and necessarily, smaller contributions from colloidosmotic forces to fluid influx in burned relative to healthy dermis. Concomitant increases in HP and in water activity implicate local changes in interfacial and metabolic energy as the source of excess fluid-transfer potential. These ex vivo findings also show that these additional forces contributing to abnormal fluid-transfer in burned skin develop independently of inflammatory and systemic hydrodynamic responses.

Water-soluble magnetic CoO nanocrystals functionalized with surfactants as T2-weighed MRI contrast agents in vitro

CoO nanocrystals (CoO NCs) were synthesized by thermal decomposition of the cobalt-oleate complex. For biological applications, water-soluble CoO NCs were obtained via a facile phase-transfer method by employing amphiphilic surfactants, such as anionic (sodium dodecyl sulfate, SDS), neutral (Pluronic F127, PF127) and cationic (cetyltrimethyl ammonium bromide, CTAB). Field-dependent magnetization measurements indicated that the type of surfactants around the CoO NCs plays a crucial role in their magnetic properties. Among them, CoO NCs functionalized with PF127 have the largest saturated magnetization (M(s)) of 10.9 emu g(-1). To clarify the potential application in magnetic resonance imaging (MRI), longitudinal relaxivities (r(1)) and transverse relaxivities (r(2)) of the functionalized CoO NCs were investigated in detail. The r(2)/r(1) of CoO NCs functionalized with PF127 is about 26. Therefore, they should be novel excellent potential T(2) contrast agents. Furthermore, methyl thiazolyl tetrazolium (MTT) assays show that they have low cytotoxicity in living cells. In vitro experiment results indicated that they can be taken up by living cells effectively, showing the obvious decrease of the transverse relaxation time T(2) after internalization.

Visualization of normal intra-parotid facial nerve on MR: BTFE or GRASS?

The facial nerve is an important surgical landmark in parotid surgery and must be preserved in superficial conservative parotidectomy.1 Therefore, accurate preoperative localization of the facial nerve is essential. Among all available imaging modes, magnetic resonance imaging (MRI) offers the best visualization of the facial nerve. However, the role of traditional T1 and T2-weighed MRI in the identification of the facial nerve is controversial 2 and various sequences, such as gradient recalled acquisition at the steady state (GRASS) and balanced turbo field echo (BTFE) have been developed.

Unusual Diagnosis in a Child Suffering From Juvenile Alexander Disease: Clinical and Imaging Report

Alexander disease is a rare, sporadic leukoencephalopathy characterized by white-matter abnormalities with frontal predominance and, as a rule, clinically associated with megalencephaly, seizures, spasticity, and psychomotor deterioration. We describe a boy who was diagnosed as affected by anorexia nervosa because of his refusal to eat, progressive weight loss, and psychologic disturbances. The observation of a hyperintense lesion on T(2)-weighed magnetic resonance images (MRIs) was initially explained as a pontine and extrapontine myelinolysis related to malnutrition. Following MRI and DNA analysis, we diagnosed a juvenile type of Alexander disease. Therefore, we can affirm the importance of the history and clinical examination to look for brainstem dysfunction in patients presenting with atypical anorexia nervosa.

Uterotubal transport disorder in adenomyosis and endometriosis—a cause for infertility

Uterine hyperperistalsis and dysperistalsis are common phenomena in endometriosis and may be responsible for reduced fertility in cases of minimal or mild extent of disease. Since a high prevalence of adenomyosis uteri has been well documented in association with endometriosis, we designed a study to examine whether hyperperistalsis and dysperistalsis are caused by the endometriosis itself or by the adenomyotic component of the disease. A prospective observational study. University hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 300 in vitro fertilisation/intracytoplasmatic sperm injection cycles and 350 intrauterine insemination cycles/year. Forty-one subjects with infertility and with laparoscopically proven endometriosis and patent fallopian tubes. Thirty-five subjects (85%) additionally showed signs of adenomyosis. All subjects underwent T2-weighed magnetic resonance imaging (MRI) and hysterosalpingoscintigraphy (HSSG) during the subsequent menstrual cycle. MRI revealed the extent of the adenomyotic component of the disease and the integrity of uterotubal transport capacity was evaluated by HSSG. Influence of adenomyosis on uterotubal transport capacity in endometriosis. In 35 of the 41 subjects (85%) with endometriosis, signs of adenomyosis were detected using T2-weighed MRI. Two of six (33%) subjects with no adenomyosis (group I) showed dysperistalsis and hyperperistalsis, compared with 14 of 24 (58%) women with focal adenomyosis (group II) and 10 of 11 (91%) women with diffuse adenomyosis (seven showed a failure in transport capacity and two contralateral transport). Our data suggest that endometriosis is associated with impeded hyperperistaltic and dysperistaltic uterotubal transport capacity. However, adenomyosis is of even more importance, especially when diffuse adenomyosis is detected. Both forms of adenomyosis are commonly found in subjects with mild to moderate endometriosis. We suggest that the extent of the adenomyotic component in subjects with endometriosis explains much of the reduced fertility in subjects with intact tubo-ovarian anatomy.

Trimodal Cancer Treatment: Beneficial Effects of Combined Antiangiogenesis, Radiation, and Chemotherapy

It has been suggested that chemotherapy and radiotherapy could favorably be combined with antiangiogenesis in dual anticancer strategy combinations. Here we investigate the effects of a trimodal strategy consisting of all three therapy approaches administered concurrently. We found that in vitro and in vivo, the antiendothelial and antitumor effects of the triple therapy combination consisting of SU11657 (a multitargeted small molecule inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases), Pemetrexed (a multitargeted folate antimetabolite), and ionizing radiation were superior to all single and dual combinations. The superior effects in human umbilical vein endothelial cells and tumor cells (A431) were evident in cell proliferation, migration, tube formation, clonogenic survival, and apoptosis assays (sub-G1 and caspase-3 assessment). Exploring potential effects on cell survival signaling, we found that radiation and chemotherapy induced endothelial cell Akt phosphorylation, but SU11657 could attenuate this process in vitro and in vivo in A431 human tumor xenografts growing s.c. on BALB/c nu/nu mice. Triple therapy further decreased tumor cell proliferation (Ki-67 index) and vessel count (CD31 staining), and induced greater tumor growth delay versus all other therapy regimens without increasing apparent toxicity. When testing different treatment schedules for the A431 tumor, we found that the regimen with radiotherapy (7.5 Gy single dose), given after the institution of SU11657 treatment, was more effective than radiotherapy preceding SU11657 treatment. Accordingly, we found that SU11657 markedly reduced intratumoral interstitial fluid pressure from 8.8 +/- 2.6 to 4.2 +/- 1.5 mm Hg after 1 day. Likewise, quantitative T2-weighed magnetic resonance imaging measurements showed that SU11657-treated mice had reduced intratumoral edema. Our data indicates that inhibition of Akt signaling by antiangiogenic treatment with SU11657 may result in: (a) normalization of tumor blood vessels that cause prerequisite physiologic conditions for subsequent radio/chemotherapy, and (b) direct resensitization of endothelial cells to radio/chemotherapy. We conclude that trimodal cancer therapy combining antiangiogenesis, chemotherapy, and radiotherapy has beneficial molecular and physiologic effects to emerge as a clinically relevant antitumor strategy.

Rat middle cerebral artery occlusion: Correlations between histopathology, T2-weighted magnetic resonance imaging, and behavioral indices

During attempts to develop the intraluminal suture model of transient middle cerebral artery occlusion (MCAO) in the Sprague Dawley strain of rats, we noticed a wide variability in lesion size seen with T2-weighed magnetic resonance imaging (MRI) or histopathology, as well as in scores for behavioral indices. It was our intent to examine the results of the study carefully and determine whether there were strong point-to-point correlations between the degree of lesion size determined from T2-weighted MRI or histopathology and intermediate or long-term neurologic/behavioral assessments. Baseline behavioral scores for forelimb dexterity (staircase test) were obtained on all animals in the period before receiving 60 minutes of transient MCAO. After MCAO, animals were tested at specified intervals from 1 to 21 days for composite neurologic deficits. T2-weighted MRI was taken at 2 and 7 days post-MCAO. At 30 and 60 days post-MCAO, animals were retested in the staircase test with subsequent histopathologic examination of the brains. Indeed, there were highly significant correlations between lesion size determined by MRI and histopathology. The damage observed in the T2-weighted MRI, as well as the size of the histopathologic lesions, were in turn highly correlated to deficiencies observed in the composite neurologic assessments, as well as to deficits at 30 and 60 days post-MCAO for skilled use of the contralateral forepaw (damaged side). In the latter test, the correlations were somewhat less significant for the ability of rats to reach for food with the ipsilateral forepaw (undamaged side). Copyright © 2001 by National Stroke Association

Fast Spin‐Echo, Magnetic Resonance Imaging‐Measured Hippocampal Volume: Correlation with Neuronal Density in Anterior Temporal Lobectomy Patients

To assess the value of magnetic resonance imaging (MRI)-measured hippocampal volume in the detection of hippocampal sclerosis, we studied 28 patients undergoing anterior temporal lobectomy for medically intractable mesial temporal lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were performed using fast spin-echo T2-weighed MRI. Quantitative neuronal density measurements were performed in the resected hippocampal specimens. There was a significant correlation between MRI-measured absolute hippocampal volume (AHV) and neuronal density in CA1, CA2, and CA3 subfields (p < 0.0001, p < 0.01, and p < 0.05, respectively). Differential hippocampal volume (side-to-side volume difference) failed to detect bilateral atrophy in three patients, but the bilateral hippocampal atrophy was recognized by considering AHV in these patients. This study suggests that MRI-measured AHV can be of value in elevating patients with mesial temporal lobe epilepsy, especially when there is no side-to-side difference in hippocampal volumetry.