Series Of MRI Research Articles

Diffusion-Weighted MRI for Response Assessment During Radiation Therapy of Lung Cancer

Diffusion-weighted MRI (DW-MRI) has recently been integrated into clinical practice to monitor tumor response to therapy in various tumor sites. However, there is only very limited data available on DW-MRI of lung cancer. The apparent diffusion coefficient (ADC), derived from DW-MRI images, is related to the mobility of water molecules and the tissue composition, including cell size, density, and integrity. In this study, changes of the ADC signal during chemoradiation therapy for lung cancer are assessed to determine the value of ADC as a predictor for response and radioresistance. Five patients with locally advanced non-small cell lung cancer (3 squamous cell cancer, 2 adenocarcinoma) underwent three series of MRI with DW-MRI and 4D CT imaging prior to, after 30 Gy, and after 60 Gy of chemoradiation therapy. Respiratory navigated DW-MRIs were acquired on a 1.5T scanner in axial planes with eight b-values ranging from 0-1000 s/mm2. Following multimodality deformable image registration, tumor (T) and affected lymph nodes (LNs) were contoured on CT, post gadolinium T1-weighted ultrafast gradient echo (VIBE), and ADC images for the purpose of comparing volumetric tumor regression and change of ADC signal with tumor response. Mean absolute ADC values and relative ADC and volume changes during radiation therapy are shown in the Table. At the end of therapy, four of five patients had partial response, and one had stable disease according to RECIST 1.1. There was no significant difference in ADC increase and VIBE or CT volume reduction between responding and non-responding patients or between tumor cell types in this small group.Oral Scientific Abstract 36; Table0 Gy0 Gy30 Gy30 Gy60 Gy60 GyTLNTLNTLNAbsolute ADC value change in m/s2 ADC (SD)1300 (423)1210 (310)1544 (388)1497 (488)1569 (469)1518 (301)ADC increase and volume decrease relative to baseline images in % ADC (SD)24 (14)22 (5)20 (9)27 (8) Volume VIBE (SD)37 (8)21 (23)60 (21)45 (29) Volume CT (SD)41 (7)14 (15)61 (6)47 (14) Open table in a new tab The preliminary results of this study show ADC signal increases early during therapy. While volume reduction continues during therapy, ADC signal does not significantly change between the 30 Gy and 60 Gy time points. Further research needs to be undertaken to investigate the predictive value of ADC signal change for tumor response, local control, and as a basis for adaptive radiation therapy planning.

Abstract TP268: Huwe1 Is Neuroprotective Against Monkey Cerebral Ischemia-reperfusion Injury By Regulating P53- And Mcl1- Dependent Apoptotic Pathways

Background: Neural cell apoptosis is one of the dominated mechanisms of cerebral ischemia-reperfusion injury (IRI). Anti-apotosis factor Mcl1 and apotosis factor p53 have been confirmed to play crucial roles in the apoptotic regulation previously. Mcl1 and p53 are the substrates of the ubiquitin ligases Huwe1, and which has been suggested as a potent therapeutic target in regulating cell apoptosis. Our aim is to explore whether Huwe1 modulates neural apoptosis by degrading Mcl1, p53 in cerebral ischemia-reperfusion injury. Methods: Eight health male adult rhesus monkeys were recruited in our study and were randomly devided into four groups: sham, PBS, siRNA silencing Huwe1 lentiviral vector and empty vector group. Except the sham group, the other groups were received corespondant intracranial injections and transient right middle cerebral occlusion (MCAO). A series of neurological evaluation and MRI were ulitized to evaluate animals. GFP flurescence was used to test transfection efficiency and apoptosis was detected by TUNEL staining. The expression level of related factors in causatum, putamen, temporal lobe and hippocampus were analyzed with western blot, QPCR, and immunohistochemistry. Results: The neurological deficit was much more serious in the silencing Huwe1 group than both empty vector and PBS group. The expression of Huwe1, Mcl1 and P53 were appeared a tendency to upregulate in the right caudatum and putament in model group than sham group in both protein and nucleotides level. Moreover, the number of apoptosis cells tested by TUNEL was the highest in the silencing Huwe 1 group, induced by decreasing expression of Huwe1 and obviously upragulating P53 expression. However, none of them has significant difference in other remote positions. Conclusion: Our study provides a potential novel mechnism that Huwe1 palys an important role in regulating neural apoptosis by regadading Mcl1 and P53 in cerebral IRI. In addition, for the first time, we confirm that the anti-apoptosis factor Mcl1 engages in the pathogenesis of cerebral IRI. It is possible that Huwe1 can be a potential therapeutic target for cerebral ischemia.

MACROSCOPIC MUSCULAR MODELING BASED ON IN VIVO 4D RADIOLOGY

Due to muscular deformation and movement, standard radiology provides only a snapshot of a probably never recurring situation. The scope of this project is dynamic rendering of muscular structures, starting from 4D-radiology, namely 3D+time, to macroscopic visualization and simulation based thereon. As full real time 4D-MRI is still beyond the technical possibilities for most human muscles, we follow kind of multi level approach. The first step is the analysis of muscular tissue of cadaveric preparations where validation can be performed by direct comparison. Secondly, nearly static, but living muscular tissue is studied based on standard 3DMRI. The first step towards time dependency are ex post composed series of static MRI where the muscle goes back to relaxed position between the acquisition steps. This is followed by so called “quasi-continuous” acquisition where, though not real time, the muscle does not go back to its original state, however remains in stretched position during acquisition. The final goal is full real time data acquisition. The radiological acquisition is followed by highly detailed image processing, segmentation, and visualization where the deforming muscular tissue is subjected to direct volume rendering with special transfer functions. The applied methods are demonstrated for the flexion of a human ankle joint and deforming human upper arm musculature. The visualization techniques proved to be well suited for capturing dynamics, but additional radiological research is strongly needed. The area of application of 4D-modeling ranges from biomechanics to medical diagnosis and therapy of muscular disorders. Key words: 4D-visualization, dynamic MRI, sequential MRI, upper arm musculature, ankle joint flexion, lower leg musculature, biceps brachii muscle, gastrocnemius muscle, direct volume rendering, 3D-reconstruction

Educational neuroscience: The early years

As developmental cognitive neuroscience explores mechanisms of change at the cognitive and neural systems level, a focus is beginning to emerge on the role of educational experiences in shaping the specific functional circuits that give rise to complex cognitive skills such as reading or math. Such studies mark the emergence of educational neuroscience. This interdisciplinary field tackles questions that stretch beyond the normal boundaries of what neuroscience or education research alone can address. In doing so, it pursues insights that are of potential value to the goals of both fields of inquiry. The report by Brem et al. (1) in this issue of PNAS falls squarely within this interdisciplinary area by studying changes in the brain activity of kindergarten children across a series of several functional MRI (fMRI) scans as they engage in different educational activities between each scan.

Menstrual Abnormalities in a Woman with Acth-Dependent Pituitary Macroadenoma Mimicking Polycystic Ovary Syndrome

Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year, but gradually failed to induce menses. She was advised to visit the endocrinology department for secondary amenorrhea and endocrine survey. Physical examination revealed central obesity, supraclavicle fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25 microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value). Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI. The patient received staging surgery including transsphenoidal adenomectomy and right frontotemporal craniotomy. As a result, the patient's physical condition gradually improved, and her menstrual cycle became regular with medication after the operation in the outpatient follow-up. PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.

In vivo assessment of NuvaRing® placement

NuvaRing®, a combined contraceptive vaginal ring 54 mm in diameter, offers many advantages over oral contraceptives. To better delineate in vivo placement, we performed MRI to confirm its anatomical position. Two healthy users, one nulliparous and one parous, underwent a series of MRI: preinsertion, immediately postinsertion and after ambulation. Three-dimensional imaging of the human vagina demonstrates that in vivo, NuvaRing® is located superior to the urogenital diaphragm (UGD), surrounding the cervix. The superior-most aspect of the ring lies behind (posterior) the cervix, at a level superior to the external os. The inferior aspect of the ring also lies in the vaginal canal above the UGD. The entire cervix rests inside the ring. The preambulation image in the nulliparous woman was the only exception. In this case, the upper portion of the ring was at the level of the lower-mid cervix and the lower aspect below the UGD. After ambulation, the ring moved cephalad and surrounded the cervix. In all instances, ambulation resulted in lower aspect of NuvaRing® moving away from the introitus. In vivo, NuvaRing® is compressed laterally forming a gentle oval in the anterior–posterior direction (5–7 mm longer than wide), an effect that is seen more in nulliparous women.

Attentional responses to unattended stimuli in human parietal cortex

Right-sided parietal lesions lead to lateralized attentional deficits which are most prominent with bilateral stimulation. We determined how an irrelevant stimulus in the unattended hemifield alters attentional responses in parietal cortex during unilateral orienting. A trial consisted of a central spatial cue, a delay and a test phase during which a grating was presented at 9 degrees eccentricity. Subjects had to discriminate the orientation of the grating. The unattended hemifield was either empty or contained a second, irrelevant grating. We carried out a series of functional MRI (fMRI) studies in 35 healthy volunteers (13 men and 22 women, aged between 19 and 30 years) as well as a behavioural and structural lesion mapping study in 17 right-hemispheric lesion patients, 11 of whom had neglect. In the patients with but not in those without neglect, the addition of a distractor in the unattended hemifield significantly impaired performance if attention was directed contralesionally but not if it was directed ipsilesionally. In the healthy volunteers, we discerned two functionally distinct areas along the posterior-anterior axis of the intraparietal sulcus (IPS). The posterior, descending IPS segment in both hemispheres showed attentional enhancement of responses during contralateral attentional orienting and was unaffected by the presence of an irrelevant stimulus in the ignored hemifield. In contrast, the right-sided horizontal IPS segment showed a strong attentional response when subjects oriented to a stimulus in the relevant hemifield and an irrelevant stimulus was simultaneously present in the ignored hemifield, compared with unilateral stimulation. This effect was independent of the direction of attention. The symmetrical left-sided horizontal IPS segment showed the highest responses under the same circumstances, in combination with a contralateral bias during unilateral stimulation conditions. None of the six patients without neglect had a lesion of the horizontal IPS segment. In four of the 11 neglect patients, the lesion overlapped with the horizontal IPS activity cluster and lay in close proximity to it in another four. The remaining three patients had a lesion at a distance from the parietal cortex. Our findings reconcile the role of the IPS in endogenous attentional control with the clinically significant interaction between direction of attention and bilateral stimulation in right parietal lesion patients. Functional imaging in neglect patients will be necessary to assess IPS function in those cases where the structural lesion spares the middle IPS segment.

Spatially encoded NMR and the acquisition of 2D magnetic resonance images within a single scan

An approach that enables the acquisition of multidimensional NMR spectra within a single scan has been recently proposed and demonstrated. The present paper explores the applicability of such ultrafast acquisition schemes toward the collection of two-dimensional magnetic resonance imaging (2D MRI) data. It is shown that ideas enabling the application of these spatially encoded schemes within a spectroscopic setting, can be extended in a straightforward manner to pure imaging. Furthermore, the reliance of the original scheme on a spatial encoding and subsequent decoding of the evolution frequencies endows imaging applications with a greater simplicity and flexibility than their spectroscopic counterparts. The new methodology also offers the possibility of implementing the single-scan acquisition of 2D MRI images using sinusoidal gradients, without having to resort to subsequent interpolation procedures or non-linear sampling of the data. Theoretical derivations on the operational principles and imaging characteristics of a number of sequences based on these ideas are derived, and experimentally validated with a series of 2D MRI results collected on a variety of model phantom samples.

Axonal lesions in multiple sclerosis: an old story revisited

The paper by Lovas et al. (2000) published in this issue of Brain is the latest in a series of studies dealing with axonal pathology in multiple sclerosis lesions. The recent re-emergence of interest by researchers in this aspect of multiple sclerosis pathology may at first seem to be at odds with the concept that defines multiple sclerosis as an inflammatory demyelinating disease of the central nervous system with (relatively) spared axons. The recognition that axonal damage occurs in multiple sclerosis lesions is, however, not new, as several of the classical studies documented axonal degeneration, described the presence of Wallerian degeneration and even attempted to quantitate axonal loss. The recent renaissance of interest in the axonal aspect of multiple sclerosis pathology has been chiefly initiated by a series of MRI, MR-spectroscopy and magnetization transfer imaging studies, which for the first time have provided non-invasive probes of pathology (McDonald, 1994; Davie et al. , 1995; Losseff et al. , 1996; Davie et al. , 1999). Several such studies have raised the possibility that (i) axonal pathology may be an early feature of multiple sclerosis, (ii) axon loss is likely to be a major cause of patients' permanent disability, and (iii) axonal pathology can be the major determinant of the development of the secondary …