Non-enhancing Regions Research Articles

Vascular Effects of Microbubble-Enhanced, Pulsed, Focused Ultrasound on Liver Blood Perfusion

The purpose of this study was to investigate the vascular effects of microbubble-enhanced pulsed high-pressure ultrasound on liver blood perfusion. In the presence of circulating lipid-shell microbubbles, a focused ultrasound transducer was used to transcutaneously treat eight livers of healthy rabbits for perfusion analysis and to treat three livers with the abdomen open for histologic analysis. Twenty-two livers treated with the ultrasound only ( n = 11) or microbubbles only ( n = 11) served as the controls. The focused ultrasound was operated at a frequency of 1.22 MHz with a peak negative pressure of 4.6 MPa. The liver blood perfusion was estimated by performing contrast-enhanced ultrasound and gray-scale quantification on the livers before and after treatment. A temporary, nonenhanced region occurred in all of the experimental livers. The regional contrast gray-scale values of the experimental group dropped significantly from 88.4 before treatment to 2.7 after treatment. The liver perfusion also demonstrated a gradual recovery over a 60-min period. The liver perfusion of the control groups remained the same after treatment. We found microvascular rupture, hemorrhage and swelling hepatocytes upon histologic examination of the experimental group. Regional liver blood perfusion can be temporarily blocked by microbubble-enhanced focused ultrasound with high-pressure amplitude. These vascular effects can be explained as acute microvascular injury of the liver and may have clinical implications.

Heterogeneity in longitudinal evolution of ring‐enhancing multiple sclerosis lesions

We enjoyed reflecting upon the article by Gaitan and colleagues, “Evolution of the Blood-Brain Barrier in Newly Forming MS Lesions”.1, 2 While the cause of MS remains unknown, a better understanding of lesion formation may provide critical clues as to the inciting event. This group has helped rekindle the debate concerning the role of blood vessels in short term lesion evolution for the 21st century. Neuropathologists have found that not all lesions have a central vessel, and lesions can be eccentric from one or multiple vessels.3, 4 Lesions may emanate from a single central nidus, grow by coalescence of periphlebitic branches, or a combination.4, 5 Our own observations based upon monthly, co-registered MRI scans using triple-dosed gadolinium (Gd, 0.3 mmol/kg, 40 min delay, 3T, 3 mm slice thickness) suggest several patterns of ring enhancing lesion (REL) development and resolution over weeks to months.6 Preceding ring formation, a nodule may appear which will later become the non-enhanced region in the ring’s center (Figure A1–5). This may be consistent with Gaitan’s suggestion of an expanding wave of inflammation recruiting additional vessels, with subsequent closure of the blood-brain barrier (BBB) within the lesion center. Figure All enhancing lesions are new, based upon normal prior month scan. A. Nodular lesion (A2) evolves the next month into the hypointense center of a REL (A3). The ring progressively fades over 2 months (A3–A5) and disappears the following month (not ... Different patterns of ring resolution may suggest heterogeneity in the subsequent cascade of immunologic events. Often, the ring will fade over months until it is no longer apparent (Figure A1–5). However, we have also observed a ring returning to a nodule (Figure B1–5, C1–3), a ring fading from the inside to the outer rim (Figure D1–3), an expanding ring (Figure E1–4), and a ring that develops several months after nodule resolution (Figure F1–5). Interestingly, multiple resolution patterns can occur within the same individual. Important questions remain as to why some MS lesions in some patients form rings. Why is the Gd concentration restricted from the lesion center? Are vessels becoming occluded as Gaitan and colleagues suggest? Or can this be coordinated reconstitution of the BBB? Is the ring an expanding wave of indiscriminate inflammation, or may it represent a strategy to limit inflammatory infiltration with continued surveillance and even repair. Most critically, why does a lesion form in the first place? Is it due to an intrinsic process within the brain parenchyma (“inside in”), or from immune cells entering from the periphery (“outside in”)?7 Multiple unanswered questions about lesion origin continue to plague the MS community. We agree that imaging should continue to help answer more of these questions.8

Progressive Aphasia and Vision Loss in a Teen-Aged Girl

A 16-year-old female honor student presented for evaluation of vertigo, headache, mild aphasia, and blurred vision. Her symptoms started approximately 2 months earlier when she experienced 3–4 days of intense vertigo and ear pain that waxed and waned and then gradually subsided. Her bifrontal headache initially was intermittent, but over the next several months, increased in severity and duration and by the time of presentation had become persistent. Her family indicated that she understood language normally but was having increasing difficulty with word finding. Visual symptoms were vaguely characterized as blurriness with intermittent diplopia. She occasionally stumbled while walking, which she attributed to difficulty seeing. She had no significant medical history. The patient was assessed at another hospital where brain MRI was abnormal. Lumbar puncture revealed a protein of 53 mg/dL (normal, 14–45 mg/dL), glucose of 36 mmol/L (normal, 50–80 mmol/L), 1 leukocyte, and 1 erythrocyte. The opening pressure was not recorded, and cytological examination was not performed. IgG index was normal, and oligoclonal bands were absent. Other unremarkable CSF studies included polymerase chain reaction (PCR) for herpes simplex viruses 1 and 2, cytomegalovirus, and JC virus, assay for myelin basic protein, and staining for acidfast bacillus. Serologic and blood studies were negative or normal, including white blood cell count, hemoglobin, hematocrit, platelet count, ferritin level, angiotensin-converting enzyme, anti-nuclear antibody, single-stranded DNA, double-stranded DNA antibody, PCR for human immunodeficiency virus, rapid plasma reagin, rheumatoid factor, very long-chain fatty acids, Lyme disease, and aquaporin-4 channel antibodies. When evaluated at our institution, the patient’s visual acuity was 20/20 in each eye with no relative afferent pupillary defect. Extraocular motility showed slight limitation of abduction of the left eye. External examination, anterior segment examination, and intraocular pressure were normal in both eyes. Dilated fundus examination revealed moderate bilateral optic disc swelling (Fig. 1). There was no evidence of vitritis or other posterior segment abnormalities. Automated perimetry revealed a right homonymous hemianopia and a left inferior homonymous quadrantanopia (Fig. 2). The patient had normal vital signs and was afebrile. No abnormalities were found on general physical examination. Neurologic examination revealed normal sensation and strength in the face and extremities. Cerebellar function, deep-tendon reflexes, and gait were normal. The patient’s speech was moderately fluid with poor naming of lowfrequency objects. Comprehension was moderate with slowing during 3-step commands. Reading was poor, and she was able to write only simple sentences. Brain MRI was obtained.

Dark Regions of No-Reflow on Late Gadolinium Enhancement Magnetic Resonance Imaging Result in Scar Formation After Atrial Fibrillation Ablation

The aim of this study was to assess acute ablation injuries seen on late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) immediately post-ablation (IPA) and the association with permanent scar 3 months post-ablation (3moPA). Success rates for atrial fibrillation catheter ablation vary significantly, in part because of limited information about the location, extent, and permanence of ablation injury at the time of procedure. Although the amount of scar on LGE MRI months after ablation correlates with procedure outcomes, early imaging predictors of scar remain elusive. Thirty-seven patients presenting for atrial fibrillation ablation underwent high-resolution MRI with a 3-dimensional LGE sequence before ablation, IPA, and 3moPA using a 3-T scanner. The acute left atrial wall injuries on IPA scans were categorized as hyperenhancing (HE) or nonenhancing (NE) and compared with scar 3moPA. Heterogeneous injuries with HE and NE regions were identified in all patients. Dark NE regions in the left atrial wall on LGE MRI demonstrate findings similar to the "no-reflow" phenomenon. Although the left atrial wall showed similar amounts of HE, NE, and normal tissue IPA (37.7 ± 13%, 34.3 ± 14%, and 28.0 ± 11%, respectively; p = NS), registration of IPA injuries with 3moPA scarring demonstrated that 59.0 ± 19% of scar resulted from NE tissue, 30.6 ± 15% from HE tissue, and 10.4 ± 5% from tissue identified as normal. Paired t-test comparisons were all statistically significant among NE, HE, and normal tissue types (p < 0.001). Arrhythmia recurrence at 1-year follow-up correlated with the degree of wall enhancement 3moPA (p = 0.02). Radiofrequency ablation results in heterogeneous injury on LGE MRI with both HE and NE wall lesions. The NE lesions demonstrate no-reflow characteristics and reveal a better predictor of final scar at 3 months. Scar correlates with procedure outcomes, further highlighting the importance of early scar prediction.

Correlation of Immunohistologic and Perfusion Vascular Parameters with MR Contrast Enhancement Using Image-guided Biopsy Specimens in Gliomas

The purpose of this study was to correlate the status of magnetic resonance contrast enhancement with immunohistologic vascular parameters such as microvascular cellular proliferation (MVCP), microvascular density (MVD), vascular endothelial growth factor receptor-2 (VEGFR-2) expression, and World Health Organization (WHO) grade obtained from image-guided biopsy specimens. We also compared perfusion computed tomography (PCT) parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and permeability surface area-product (PS) with the presence or absence of contrast enhancement. A total of 26 image-guided biopsy specimens in 16 patients with treatment naive gliomas were obtained from contrast-enhancing (CE) and nonenhancing (NE) regions of the glioma. Contrast enhancement status was correlated with MVD, MVCP, VEGFR-2 expression, and WHO grade obtained from the biopsy specimen as well as with the PCT parameters. Contrast enhancement showed statistically significant correlation with MVCP (P = .003) and PS (P = .007) when compared with various immunohistologic and perfusion vascular parameters. WHO grade of the biopsy specimen showed statistically significant correlation with contrast enhancement (P = .002), MVCP (P < .001), and PS values (P = .028). Contrast enhancement in gliomas is primarily from a break in blood-brain barrier as evidenced by its correlation with PS and MVCP, whereas it was not statistically correlated with CBV and MVD even though it showed a positive trend. Contrast enhancement also showed significant correlation with WHO grade suggesting a biopsy from CE region in a heterogeneous glioma probably will still yield the most aggressive part of the glioma is also shown by its association with MVCP and PS estimates.

Short-term results of magnetic resonance imaging-guided focused ultrasound surgery for patients with adenomyosis: symptomatic relief and pain reduction

The objective of this study was to evaluate the degree of symptomatic relief obtained after treatment with magnetic resonance-guided focused ultrasound surgery in patients with adenomyosis. Quality of life and pain assessment questionnaires from 35 women, collected on the day of treatment and up to 6 months after treatment, indicated that the treatment was safe and there was a significant reduction in symptoms.

Comparison between Population Average and Experimentally Measured Arterial Input Function in Predicting Biopsy Results in Prostate Cancer

To test whether individually measured arterial input function (AIF) provides more accurate prostate cancer diagnosis then population average AIF when dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data are acquired with limited temporal resolution. Twenty-six patients with a high clinical suspicion for prostate cancer and no prior treatment underwent DCE MRI examination at 3.0 T before biopsy. DCE MRI data were fitted to a pharmacokinetic model using three forms of AIF: an individually measured, a local population average, and a literature double exponential population average. Receiver operating characteristic (ROC) analysis was used to correlate MRI with the biopsy results. Goodness of fit (chi(2)) for the three AIFs was compared using nonparametric Mann-Whitney test. Average volume transfer constant (K(trans)) values were significantly higher in tumor than in normal peripheral zone for all three AIFs. The individually measured and the local population average AIFs had the highest sensitivity (76%), whereas the double exponential AIF had the highest specificity (82%). The areas under the ROC curves were not significantly different between any of the AIFs (0.81, 0.76, and 0.81 for the individually measured, local population average, and double exponential AIFs, respectively). chi(2) was not significantly different for the three AIFs; however, it was significantly higher in enhancing than in nonenhancing regions for all three AIFs. These results suggest that, when DCE MRI data are acquired with limited temporal resolution, experimentally measured individual AIF is not significantly better than population average AIF in predicting the biopsy results in prostate cancer.

Safety and Efficacy of High Intensity Focused Ultrasound Ablation Therapy for Adenomyosis

In patients with adenomyosis, the severity of symptoms correlates roughly with the extent of adenomyosis. Thus, it was hypothesized that the ablation of enough volume of adenomyosis might alleviate symptoms. The aim of this study was to investigate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation for the treatment of adenomyosis. Phase I HIFU ablation of adenomyosis was performed on 12 patients. Three patients each were treated using four different acoustic intensities (290, 340, 380, and 420 W) step by step. Contrast-enhanced ultrasound was used to evaluate the necrotic region of treated adenomyosis. The efficacy of therapy was evaluated after 3 months of follow-up. All patients in the four groups tolerated the therapy well, and no severe complications were found during follow-up. After treatment, nonenhanced necrotic regions were shown on contrast-enhanced ultrasound in all treated adenomyosis. The mean volumes of the nonenhanced regions were 72, 75, 68, and 124 cm(3) in the 290-W, 340-W, 380-W, and 420-W groups, respectively. At 3 months after therapy, the mean pain relief in the four groups was 25%, 58.3%, 66.7%, and 83.3%, respectively. HIFU may be a safe and effective method to treat adenomyosis, and an acoustic intensity of 420 W may be able to produce larger volumes of necrosis and better pain relief.

Pathology and Radiology Beyond Looking at Pictures

Pathology and Radiology Beyond Looking at Pictures

Quantitative MRI assessment of uninvolved breast tissue in patients with locally-advanced breast cancer undergoing neoadjuvant chemotherapy.

Abstract Abstract #4016 Background: We studied the Magnetic Resonance Imaging (MRI) characteristics of breast tissue in patients with invasive cancers to better understand the relationship between tumors and their normal “host” tissue. There is a strong association between tumor morphologic patterns on MRI and both treatment outcome and survival. The objectives of this study were to assess the characteristics of normal host tissue to verify whether they were associated with treatment outcome.&amp;#x2028; Materials and Methods: 42 women with locally-advanced breast cancer underwent MRI exams prior to the start of neoadjuvant adriamycin/cytoxan (AC) chemotherapy (MRI1), following one cycle of AC (MRI2) and at the completion of chemotherapy, prior to surgery (MRI3). Patients mean age was 48.56 years (range 29.7 - 71.5). Median follow-up was 178 weeks. Pathology and radiology reports were available for all patients. Total follow-up was 3 years. We quantified tumor and surrounding normal tissue enhancement. Signal Enhancement Ratio (SER) values have been histopathologically shown to positively correlate with microvessel density within tumor. We lowered the enhancement threshold necessary to detect MRI tumor-enhancing regions, to insure that slow or non-enhancing tissue regions could be analyzed. For all patients, tumor morphologic patterns were categorized according to the degree of tumor containment from 1, denoting well-circumscribed uni-centric masses to 5, corresponding to infiltrative tumors with ill-defined borders. MRI breast tissue composition quantitative measures included 1) volumetric breast density, 2) tumor volume, 3) normal fibroglandular tissue volume and 4) SER levels in tumor and normal surrounding tissue. In order to quantify the uninvolved breast tissue volume, we used a semi-automated technique that performs a segmentation of MRI breast tissue from fat regions without user interaction, therefore avoiding subjective threshold decision issues. Regions in normal tissue surrounding tumors were automatically selected and analyzed at all time points.&amp;#x2028; Results: 10 patients recurred. We found that non-tumor mean SER did not change significantly with one cycle of chemotherapy, however the value of non-tumor mean SER after 1 cycle of chemotherapy was an independent predictor of disease free survival. We also observed a strong association between the initial (pre-treatment) tumor morphologic patterns on MRI with treatment outcome. We found that volume of normal breast tissue at baseline does relate to tumor phenotype (p&amp;lt;0.067), and change in non-tumor breast tissue volume after chemotherapy was also predictive of recurrence (p&amp;lt;0.075).&amp;#x2028; Conclusion: We found that measures of uninvolved breast tissue volume were correlated with tumor phenotypes and were shown to be predictive of recurrence. These results suggest that the host tissue may provide treatment response information. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4016.

Diffusion-Tensor Imaging for Glioma Grading at 3-T Magnetic Resonance Imaging

To retrospectively determine whether fractional anisotropy (FA) or mean diffusivity (MD) value at 3-T diffusion-tensor imaging is different between low- and high-grade gliomas and may be useful for glioma grading. Review board approval was obtained, and informed consent was waived. Diffusion-tensor imaging was performed in 27 patients with surgically proved gliomas (19 high-grade and 8 low-grade gliomas). Fractional anisotropy and MD values were measured in 3 regions; peritumoral edema, and enhancing and nonenhancing tumor regions. We compared mean FA and MD values of nonenhancing tumor regions between low- and high-grade gliomas and compared the FA and MD values among the 3 mentioned regions in high-grade gliomas. The relationship between FA and MD values of tumors was also investigated. Statistical analysis was performed using the Student t test and Pearson correlation coefficients. In the nonenhancing regions of tumors, FA ratios were not significantly different between low- and high-grade gliomas (0.472 and 0.701, P = 0.075), but MD ratios were significantly lower in high-grade gliomas (1.899 and 1.23, P < 0.001). In high-grade gliomas, enhancing tumors showed a tendency toward a lower FA ratio than nonenhancing tumors (P = 0.034), but FA values or ratios of peritumoral edema were not significantly different from those of enhancing or nonenhancing tumor. No strong relationship was found between FA and MD values. Fractional anisotropy values of low- and high-grade gliomas were not significantly different. However, MD values of nonenhancing low-grade gliomas were significantly higher than those of nonenhancing high-grade gliomas, which will be useful for the grading of nonenhancing infiltrative gliomas.

Evaluation of human brain tumor heterogeneity using multiple T1‐based MRI signal weighting approaches

Vascular-space-occupancy (VASO) MRI without contrast injection was explored for imaging cerebral blood volume (CBV) and tissue heterogeneity in gliomas (n = 10). VASO contrast complemented contrast-enhanced T(1)-weighted (GAD-T(1)w), FLAIR and T(1)w magnetization-prepared-rapid-gradient-echo (MPRAGE) images. High-grade gliomas showed a VASO-outlined hyperintense zone corresponding to long-T(1) regions in MPRAGE and to nonenhancing regions in GAD-T(1)w images. FLAIR, MPRAGE, and VASO data were used to segment tumors into multiple zones of different T(1). After removal of known resection areas using pre- and postsurgical MRI, the volume of overlap between the hyperintense VASO-zone and the long-T(1) MPRAGE zone correlated with that of GAD-T(1)w enhancement (R(2) = 0.99) and tumor grade. Based on these correlations, this remaining long T(1) overlap area was tentatively assigned to necrosis. In one promising case the collective T(1)-weighted approach accurately identified a low-grade glioma despite the presence of contrast enhancement in GAD-T(1)w images consequential to chemoradiation-associated treatment effect. The results suggest that this collective T(1)-weighted approach may provide useful information for regional assessment of heterogeneous tumors and for guiding treatment-related decisions in patients with gliomas.

Soft X-ray Resonant Magnetic Reflectivity Study on Induced Magnetism in [Fe70Co30/Pd]nSuper-Lattice Films

We performed soft x-ray resonant magnetic reflectivity experiments on [FeCo/Pd]n super-lattice films to study the depth profile of magnetization near the interface. From the analysis of the reflectivity measured at the Fe-LIIIabsorption edge, we obtained the magnetization profiles for the samples with different FeCo layer thicknesses. The profiles can be divided into three different zones: (A) Mixed region at the Pd interface where the magnetization decreased due to the structural randomness, (B) Enhanced region where the magnetization increased, and (C) Non-enhanced region. We estimated the thickness where the FeCo magnetization is enhanced by the adjacent Pd layer is about 4 atomic monolayers.

Experimental study of single-phase pressure drop and heat transfer in a micro-fin tube

The single-phase pressure drop and heat transfer in a micro-fin tube were measured using oil and water as the working fluids. The Prandtl number varied from 3.2 to 220 and the Reynolds number ranged from 2500 to 90,000. The results show that there is a critical Reynolds number, Re cr , for heat transfer enhancement. For Re < Re cr , the heat transfer in the micro-fin tube is the same as that in a smooth tube, but for Reynolds numbers higher than Re cr , the heat transfer in the micro-fin tube is gradually enhanced compared with a smooth tube. It reaches more than twice that in a smooth tube for Reynolds numbers greater than 30,000 with water as the working fluid. The Nusselt number is proportional to Pr 0.56 in the enhanced region and is proportional to Pr 0.3 in the non-enhanced region. For the high Prandtl number working fluid (oil, 80 < Pr < 220 ), the critical Reynolds number for heat transfer enhancement is about 6000, while for the low Prandtl number working fluid (water, 3.2 < Pr < 5.8 ), the critical Reynolds number for heat transfer enhancement is about 10,000. The friction factors in the micro-fin tube are almost the same as for a smooth tube for Reynolds numbers below 10,000. For Reynolds numbers higher than 30,000, the friction factor is about 40–50% higher than for a smooth tube.

Perfusion, diffusion and spectroscopy values in newly diagnosed cerebral gliomas

To evaluate perfusion, diffusion, and spectroscopy values in enhancing and non-enhancing lesions for patients with newly diagnosed gliomas of different grades. Sixty-seven patients with newly diagnosed glioma were entered into the study 20 grade II, 26 grade III and 21 grade IV. MR data were acquired at 1.5T and included diffusion weighted images (59/67 patients), dynamic perfusion weighted images (30/67 patients) and 3D H-1 MR spectroscopy (64/67 patients). Enhancing and non-enhancing lesions were delineated by a neuroradiologist and applied to maps of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC), relative anisotropy (RA) and metabolite intensities. The median rCBV within enhancing regions of grade IV gliomas was significantly elevated relative to enhancing regions in grade III gliomas and normal brain. ADC was elevated relative to normal brain, but was not significantly different between grades or between enhancing and non-enhancing regions. The RA was higher in the non-enhancing region of grade IV gliomas relative to grade II and grade III. Levels of lactate plus lipid were significantly elevated in grade IV relative to grade II and grade III gliomas. Both enhancing and non-enhancing regions in grade IV gliomas showed significant correlations between CBV, ADC and choline levels. The data were consistent with grade IV gliomas having higher membrane turnover, increased cell density and increased vascularity within enhancing lesions. Analysis of the correlations among parameters within grade IV gliomas suggested that high vascularity (high rCBV) was correlated with increased cellularity (low ADC) and increased membrane turnover (high choline) in these lesions. The non-enhancing region of grades II and III gliomas had MR parameters consistent with increased cellularity and/or membrane turnover.

Is There a Role for Apparent Diffusion Coefficients in the Differential Diagnosis of Brain Tumors?

We determined the potential benefits of apparent diffusion coefficient (ADC) values of enhancing-nonenhancing solid portions, cystic-necrotic areas and surrounding edema in the differential diagnosis of brain tumors. Eighty-eight patients with brain tumors: 16 low-grade gliomas, 21 high-grade gliomas, 26 metastases and 25 meningiomas were imaged prospectively in a 1.5 Tesla magnetic resonance (MR) unit. Routine MR imaging and echo-planar diffusion-weighted imaging (DWI) with b values of 0 and 1000 mm(2)/s were performed. ADC values were obtained in different tumor parts and peritumoral edema. The ADCs of contrast-enhancing tumor regions were higher in high-grade gliomas than meningiomas (p<0.05). No significant differences were found in ADCs of contrast-enhancing regions comparing other tumor groups (p≥0.05). The ADCs in non-enhancing tumor regions did not differ between low-grade and high-grade gliomas (p≥0.05). The ADCs in cystic-necrotic regions of tumors and surrounding edema were not significantly different comparing all tumor groups (p≥0.05). There were no significant differences between ADCs of contrast-enhancing and non-enhancing regions of high-grade and low-grade gliomas (p≥0.05). No significant differences were found in ADCs of contrast-enhancing and non-enhancing areas of tumors comparing to surrounding edema (p≥0.05). ADC was not found to be useful in distinguishing different tumor types and its value in the diagnosis of brain tumors is limited due to considerable overlaps.

Contrast-enhanced sonography of pancreatic carcinoma: correlations with pathological findings

We examined contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma in relation to the pathological findings in resected specimens to evaluate correlations between observations made by this modality and the pathological findings. The pathological findings of surgical specimens obtained from 16 patients were examined in relation to the contrast-enhanced harmonic gray-scale sonography findings. Lesion vascularity was examined by contrast-enhanced harmonic gray-scale sonography from 20 to 50 s after the injection of Levovist (Schering, Berlin, Germany) (early phase), and lesion enhancement was also monitored at approximately 90 s after injection (delayed phase). Contrast-enhanced harmonic gray-scale sonography showed positive enhancement in 12 of the 16 lesions (peripheral tumor region alone, n = 9; entire tumor, n = 3), while the other 4 lesions showed no contrast enhancement in any region. Twelve enhanced regions (9 peripheral tumor region and 3 entire tumor regions) detected by contrast-enhanced harmonic gray-scale sonography showed: (1) mild fibrosis with inflammation, in 10 regions (83%); (2) the presence of both carcinoma cells and residual acinar cells in 8 (67%); and (3) presence of relatively large arteries in 2 (17%). In contrast, 13 non-enhanced regions (4 entire tumor regions and 9 central regions) showed: (1) severe fibrosis in 10 regions (77%); (2) necrosis in 7 (54%); and (3) mucin in 4 (31%). Contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma are influenced by interstitial histological features associated with tumor growth.

Medullomyoblastoma: a radiographic and clinicopathologic analysis of six cases and review of the literature.

Medullomyoblastoma (MMB) is a rare cerebellar embryonal neoplasm that occurs almost exclusively in children. It is biphasic by microscopy, containing myoblastic and primitive neuroectodermal components. The authors conducted a retrospective review of the radiographic and pathologic characteristics, treatment, and clinical outcomes of six children with MMB who were treated at St. Jude Children's Research Hospital (Memphis, TN) between 1984 and 2003. Fluorescence in situ hybridization (FISH) data were available for four children. A literature review also was conducted and focused on imaging and pathologic findings. The median age at diagnosis was 4.5 years (range, 0.83-7.5 years). Radiographically, all tumors were cerebellar and exhibited variable enhancement, and 50% of tumors had necrotic foci. Three tumors contained discrete, magnetic resonance imaging (MRI) T2-weighted-hypointense/computed tomography (CT)-hyperdense enhancing regions and separate hyperintense/hypodense nonenhancing regions, which correlated microscopically with geographic islands of primitive neuroectodermal and rhabdomyoblastic cells. Large cell/anaplastic (five tumors), nodular/desmoplastic (two tumors), and classic (two tumors) medulloblastoma histologies were encountered either alone (five tumors) or in combination with each other (two tumors). All 4 tumors that were tested exhibited alterations in chromosome 17 or c-myc amplification. All patients underwent macroscopic total resection and subsequently received chemotherapy and craniospinal (five patients) or local conformal (one patient) radiotherapy. At a median follow-up of 92 months (range, 23-187 months), 3 patients remain alive with no evidence of disease, 2 patients have died of disease, and 1 patient has died of secondary acute lymphocytic leukemia. The results of the current study demonstrated the frequent correlation of biphasic nodularity (as determined by MRI or CT) with discrete rhabdomyoblastic and primitive neuroectodermal islands (as revealed by microscopy) in MMB. These results also support the view that MMB and medulloblastoma may have common tumorigenic origins, given their similar histologic and molecular features.

Magnetic resonance image-guided proteomics of human glioblastoma multiforme.

To investigate the correlation between gadolinium contrast-enhancement patterns on T1-weighted magnetic resonance (MR) images and spatial changes in protein expression profiles in human glioblastoma multiforme (GBM) and the use of imaging as a noninvasive technique to evaluate the heterogeneity of solid tumors prior to microarray analysis. Four patients with MR images and confirmed diagnosis of GBM were enrolled in the study. Intraoperative stereotaxy was used in conjunction with MR images to identify contrast-enhanced (CE) and nonenhanced (NE) regions of the tumor during surgical resection. Total protein was extracted from resected tumor samples using standard techniques and subjected to proteomic analysis using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). We found that protein profiles from CE and NE regions within a given tumor have qualitative and semiquantitative proteomic pattern differences, suggesting an altered gene expression profile that correlates with detectable tissue imaging parameters. We also found that CE regions within the same tumor exhibited distinct differences in protein expression profiles, despite similar histological features. In addition, there were marked similarities in the proteomic patterns among the NE regions across all patients, while the CE regions were distinct, suggesting that the CE regions have complex protein profiles unique to individuals. The results demonstrate that major differences in protein expression patterns within a tumor can be correlated to radiographic findings. Image-guided proteomics holds promise for characterizing tissue prior to microarray analysis designed to identify specific diagnostic markers and therapeutic targets within solid tumors.

Comparing genomic and histologic correlations to radiographic changes in tumors: a murine SCC VII model Study 1

Rationale and Objectives. To investigate the correlation between the temporal changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging (MRI), histologic evaluation, and genomic analysis using oligonucleotide microarrays in a murine squamous cell carcinoma tumor models Materials and Methods. The squamous cell carcinoma (SCC VII) cell line was used to initiate subcutaneous tumors in mice. This mouse model has been used as a model for human head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE-MRI). Different stages of tumor growth were defined based on changes in the T1- and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE) regions of the tumors were marked and biopsied for oligonucleotide microarray and histologic analysis. Tumors with no differential contrast enhancement were used as controls. Results. Distinct temporal stages of tumor progression can be defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2-weighted images with no significant differential gene expression from the center and periphery of the tumor. The more advanced tumors that show discrete regions of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from the CE and NE regions show distinctly differential gene expression profiles. Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained from the periphery and center of the early stage tumors and the CE and NE regions from these more advanced tumors were similar. The gene expression profiles of late-stage tumors that showed changes in T2-weighted MRI signal intensity were consistent with tissue degradation in the NE region, which also showed characteristic signs of tissue necrosis in histologic analysis. Conclusion. These results show that temporal changes in T1- and T2-weighted CE-MRI are related to distinct gene expression profiles, and histologic analysis may not be sufficient to detect these detailed changes. As tumors progress, discrete regions of post-contrast T1 enhancement are identified; these regions have distinct gene expression patterns despite similar histologic features. In late-stage tumors, regions of T2 signal changes are observed which correspond with tissue necrosis.