Comparison of technical success and safety of transbronchial versus percutaneous CT-guided fiducial placement for SBRT of lung tumors.

OBJECTIVE: To evaluate the technical success and safety of transbronchial (bronchoscopic) fiducial placement compared to percutaneous CT-guided fiducial placement for stereotactic body radiotherapy (SBRT) of lung tumors. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant retrospective study was performed at a single tertiary institution. Consecutive patients undergoing lung fiducial placement for purposes of guiding SBRT (CyberKnife®, Accuray, Inc.) between September 2005 to January 2013 were included in the study. Fiducial seeds were placed percutaneously with CT guidance or transbronchially with bronchoscopic guidance. We compared procedure-related complications (pneumothorax, chest tube placement), technical success (defined as implantation enabling adequate treatment planning with CT simulation) and migration rate. The need for repeat procedures and their mode was noted. Statistical analysis was performed using Fisher exact and Chi square probability tests. RESULTS: Two hundred and forty-four patients with lung tumors and 272 fiducial seed placements were included in the study. Two hundred and twenty-one of the 272 (81.2%) fiducial markers were placed percutaneously and 51/272 (18.8%) were placed transbronchially. Pneumothorax was seen in 73/221 (33%) of percutaneously-placed fiducials and in 4/51 (7.8%) of transbronchial placements (p<0.001). No significant difference was seen in the rate of chest tube placement between the two groups: 20/221 (9%) of percutaneously placed fiducials and 2/51 (3.9%) of transbronchially placed fiducials (p=0.39). Fifteen of the 51 (29%) of fiducial placements with transbronchial approach were unsuccessful, as discovered at radiotherapy planning session, and required a repeat procedure. Nine of the 15 (60%) of repeat procedures were performed percutaneously, 5/15 (33%) were placed during repeat bronchoscopy, and 1/15 (7%) was placed at transesophageal endoscopic ultrasound. No repeat fiducial placements were required for patients who had the fiducials placed percutaneously (p<0.001), with a technical success rate of 100%. CONCLUSION: Transbronchial fiducial marker placement has a significantly higher rate of failed seed placements requiring repeat procedures in comparison to percutaneous placement. Complication rate of pneumothorax requiring chest drain placement is similar between the two approaches.

Turning on the red phosphorescence of a [Ru(tpy)(bpy)(Cl)]Cl complex by amide substitution: self-aggregation, toxicity, and cellular localization of an emissive ruthenium-based amphiphile.

Coupling the notoriously non-emissive complex [Ru(tpy)(bpy)Cl]Cl (tpy = 2,2':6',2''-terpyridine, bpy = 2,2'-bipyridine) to a C12 alkyl chain via an amide linker on the 4' position of the terpyridine yielded a new amphiphilic ruthenium complex showing red emission and chloride-dependent aggregation properties. This emissive complex is highly cytotoxic in A549 non-small lung cancer cells where it can be followed by confocal microscopy. Uptake occurs within minutes, first by insertion into the cellular membrane, and then by migration to the peri-nuclear region.

An in vitro cell irradiation protocol for testing photopharmaceuticals and the effect of blue, green, and red light on human cancer cell lines.

Traditionally, ultraviolet light (100-400 nm) is considered an exogenous carcinogen while visible light (400-780 nm) is deemed harmless. In this work, a LED irradiation system for in vitro photocytotoxicity testing is described. The LED irradiation system was developed for testing photopharmaceutical drugs, but was used here to determine the basal level response of human cancer cell lines to visible light of different wavelengths, without any photo(chemo)therapeutic. The effects of blue (455 nm, 10.5 mW cm(-2)), green (520 nm, 20.9 mW cm(-2)), and red light (630 nm, 34.4 mW cm(-2)) irradiation was measured for A375 (human malignant melanoma), A431 (human epidermoid carcinoma), A549 (human lung carcinoma), MCF7 (human mammary gland adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), and U-87 MG (human glioblastoma-grade IV) cell lines. In response to a blue light dose of 19 J cm(-2), three cell lines exhibited a minimal (20%, MDA-MB-231) to moderate (30%, A549 and 60%, A375) reduction in cell viability, compared to dark controls. The other cell lines were not affected. Effective blue light doses that produce a therapeutic response in 50% of the cell population (ED50) compared to dark conditions were found to be 10.9 and 30.5 J cm(-2) for A375 and A549 cells, respectively. No adverse effects were observed in any of the six cell lines irradiated with a 19 J cm(-2) dose of 520 nm (green) or 630 nm (red) light. The results demonstrate that blue light irradiation can have an effect on the viability of certain human cancer cell types and controls should be used in photopharmaceutical testing, which uses high-energy (blue or violet) visible light activation.

Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium prodrug offering two trans coordination sites.

In this work, two new photopharmacological ruthenium prodrugs are described that can be activated by green light. They are based on the tetrapyridyl biqbpy ligand (6,6'-bis[N-(isoquinolyl)-1-amino]-2,2'-bipyridine), which coordinates to the basal plane of the metal centre and leaves two trans coordination sites for the binding of monodentate sulphur ligands. Due to the distortion of the coordination sphere these trans ligands are photosubstituted by water upon green light irradiation. In vitro cytotoxicity data on A431 and A549 cancer cell lines shows an up to 22-fold increase in cytotoxicity after green light irradiation (520 nm, 75 J cm-2), compared to the dark control. Optical microscopy cell imaging and flow cytometry indicate that the cancer cells die via apoptosis. Meanwhile, very low singlet oxygen quantum yields (∼1-2%) and cell-free DNA binding studies conclude that light-induced cell death is not caused by a photodynamic effect, but instead by the changes induced in the coordination sphere of the metal by light, which modifies how the metal complexes bind to biomolecules.

CT findings in runner's colitis.

A spectrum of lower gastrointestinal tract symptoms occurs in marathon runners. Although most symptoms are transient, reversible ischemic colitis is a rare complication that typically responds to supportive therapy. Because computed tomographic features have not been previously described to our knowledge, we describe abdominal computed tomographic manifestations of reversible ischemic colitis in three marathon runners. On computed tomography, reversible ischemic colitis involves the cecum, with varying involvement of the proximal colon.

[Calcification of the falx cerebri. A pathognomonic symptom of Gorlin-Goltz syndrome]. / Verkalkung der Falx cerebri. Ein pathognomonisches Zeichen beim Gorlin-Goltz-Syndrom.

BACKGROUND: Gorlin-Goltz syndrome is an autosomal dominant disorder with variable penetration characterized primarily by keratocysts of the jaws, multiple basal cell carcinomas, skeletal abnormalities and intracranial calcifications. METHOD: In this study, 4787 radiographs with occipitomental x-rays from the hospital archives for oral and maxillofacial surgery of the Christian Albrechts University Kiel were examined for calcifications in the area of the falx cerebri. RESULTS: Four characteristic alterations in the falx cerebri could be assigned to four groups of structures. Those in group 4 could be found only within Gorlin-Goltz syndrome patients, and differed significantly in form and extent from the remaining three groups. CONCLUSION: The plurilamellar appearance of this group could be rated as a pathognomonic symptom of the Gorlin-Goltz syndrome.

Teardrop superior mesenteric vein: CT sign for unresectable carcinoma of the pancreas.

OBJECTIVE: Our objective was to investigate whether a tethered, teardrop-shaped superior mesenteric vein (SMV) is a reliable CT indicator of unresectable adenocarcinoma of the head of the pancreas. MATERIALS AND METHODS: CT scans of 92 patients with high suspicion for pancreatic head adenocarcinoma were retrospectively reviewed by two radiologists who were unfamiliar with the patients' outcomes. The reviewers were asked to assess whether the teardrop SMV sign was present or not; agreement was reached by consensus. Teardrop SMV was considered absent in patients with an obstructed vessel. RESULTS: Of 92 patients, 30 had a normal pancreas without a teardrop SMV. A mass in the head of the pancreas was seen in all 62 patients with cancer. Of these 62 patients, 30 (seven with teardrop SMV) were deemed to have inoperable disease by standard CT or clinical criteria. The remaining 32 patients underwent surgery; only 15 of these 32 had successful pancreatoduodenectomies. No patient with resectable tumor had an unequivocal teardrop SMV sign. In 17 patients (13 with teardrop SMV), resection of the tumor could not be accomplished because of vascular encasement (n = 12) or metastasis (n = 5). Added to conventional signs, teardrop SMV significantly increased CT's sensitivity (from 60% to 91%) and accuracy (from 79% to 95%) without significantly changing its specificity (from 100% to 98%) for resectability of pancreatic head cancer. CONCLUSION: The teardrop SMV is a reliable sign for predicting unresectability of adenocarcinoma of the head of the pancreas and can significantly contribute to preoperative planning.

The ischemic penumbra: operationally defined by diffusion and perfusion MRI.

BACKGROUND: Identifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged. OBJECTIVE: To operationally define and characterize cerebral tissue at risk for stroke progression. METHODS: We retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study. We applied a logistic regression model using maps of the relative mean transit time and relative cerebral blood flow (rCBF) as well as three different maps of the relative cerebral blood volume (rCBV) to predict an operationally defined penumbra (region of mismatch between the diffusion lesion on day 1 and its extension 24 to 72 hours later). RESULTS: Maps of the rCBF and initial rCBV were significant predictors for identifying penumbral tissue. Our operationally defined penumbral region was characterized by a reduction in the initial rCBV (47% of contralateral control region [CCR]), an increase (163% of CCR) in the total rCBV, and a reduction (37% of CCR) in the rCBF, whereas the operationally defined ischemic core showed a more severe reduction in the rCBF (12% of CCR) and in the initial rCBV (19% of CCR). CONCLUSION: These MR indexes may allow the identification and quantification of viable but ischemically threatened cerebral tissue amenable to therapeutic interventions in the hyperacute care of stroke patients.

Sonographic appearance of early complete molar pregnancies.

Since our anecdotal experience indicates that the classically described "snowstorm" appearance on ultrasonography of early molar pregnancies is often not present and that theca-lutein cysts are also rare, we examined the ultrasonographic appearance of early complete molar pregnancies. We reviewed the ultrasonographic reports and clinical data of 21 cases of histologically diagnosed complete molar pregnancies with a mean gestational age at sonography of 10.5 weeks (range, 4 to 18 weeks). The diagnosis of molar pregnancy was made on ultrasonography in 12 (57%) cases, was second in the differential diagnosis of one (4.8%) case, and was not considered in eight (38%) cases. No theca-lutein cysts were identified. Five of five (100%) molar pregnancies of 13 weeks or over were diagnosed prospectively, while only eight of 16 (50%) earlier pregnancies were correctly diagnosed prospectively. In a retrospective review of the available images of 16 patients, only nine of 16 (56%) images demonstrated the classic appearance, and no theca-lutein cysts were seen. We conclude that the classic appearance of complete moles on ultrasonography is seen in less than two thirds of cases and even less commonly in the first trimester. The prevalence of theca-lutein cysts is very low.

Echoplanar MR imaging for ultrafast detection of brain lesions.

OBJECTIVE: We retrospectively evaluated the use of echo-planar imaging for ultrafast detection of brain lesions. MATERIALS AND METHODS: In our retrospective study, 61 patients were imaged with the following echo-planar sequences: single-shot proton density-weighted, single-shot T2-weighted, single-shot T2-weighted high-resolution, multishot proton density-weighted, and multishot T2-weighted. Lesions revealed in these patients ranged from 0.5 to 12.0 cm (mean, 3.7 cm) and were the result of tumor (n = 16), stroke (n = 21), demyelination (n = 18), and toxoplasmosis (n = 2). Four patients had scans with normal findings. Two neuroradiologists who were unaware of pertinent clinical data reviewed the images. The images were retrospectively compared with conventional spin-echo images for diagnosis, sensitivity of lesion detection, and qualitative criteria: subjective image quality, gray and white matter differentiation, lesion conspicuity, delineation of lesion borders, and artifacts. (Artifacts included those caused by motion, susceptibility, pulsation, and ghosting.) Quantitative criteria, including signal-to-noise and signal difference-to-noise measurements, were also evaluated in 40 lesions. RESULTS: Sensitivity for lesion detection was 97% for single-shot echo-planar T2-weighted MR images and 100% for multishot echo-planar T2-weighted MR images. Single-shot echo-planar proton density-weighted MR images had the highest signal-to-noise ratio (91.2+/-19.3). Echo-planar T2-weighted MR images had the highest signal difference-to-noise (33.8+/-22.9). Echo-planar sequences were superior to spin-echo sequences regarding motion and pulsation artifacts. Spin-echo sequences lacked susceptibility and ghosting artifacts, and were superior in lesion conspicuity and delineation of lesion borders. CONCLUSION: In this study, echo-planar sequences were as sensitive as conventional spin-echo imaging for the diagnostic assessment of lesions. Echo-planar sequences had a strikingly shorter acquisition time and substantially reduced motion and pulsation artifacts. Echo-planar sequences may be a useful diagnostic tool for use in claustrophobic and unstable patients.

A general kinetic model for quantitative perfusion imaging with arterial spin labeling.

Recently, several implementations of arterial spin labeling (ASL) techniques have been developed for producing MRI images sensitive to local tissue perfusion. For quantitation of perfusion, both pulsed and continuous labeling methods potentially suffer from a number of systematic errors. In this study, a general kinetic model for the ASL signal is described that can be used to assess these errors. With appropriate assumptions, the general model reduces to models that have been used previously to analyze ASL data, but the general model also provides a way to analyze the errors that result if these assumptions are not accurate. The model was used for an initial assessment of systematic errors due to the effects of variable transit delays from the tagging band to the imaging voxel, the effects of capillary/tissue exchange of water on the relaxation of the tag, and the effects of incomplete water extraction. In preliminary experiments with a human subject, the model provided a good description of pulsed ASL data during a simple sensorimotor activation task.

STAR-HASTE: perfusion imaging without magnetic susceptibility artifact.

A novel magnetic resonance imaging technique (STAR-HASTE) based on pulsed arterial spin labeling using a single shot acquisition method is described for perfusion imaging. The method is similar to EPISTAR in using STAR (Signal Targeting with Alternating Radiofrequency) technique for pulsed radiofrequency labeling of inflowing blood, but uses a half-Fourier single shot turbo spin-echo (HASTE) sequence for data acquisition instead of echo-planar imaging (EPI). Our preliminary studies show that STAR-HASTE permits perfusion imaging to be performed without many of the artifacts encountered with other imaging methods based on EPI acquisition. The novel method not only provides similar perfusion information to that obtained by EPISTAR, as demonstrated in the functional brain imaging study, but also eliminates magnetic susceptibility artifacts and image distortion commonly observed in EPI images. Furthermore, this technique can be readily implemented in MR systems without EPI capability.

Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome.

Diffusion-weighted magnetic resonance imaging detects ischemic injury within minutes after onset, and has been used to demonstrate drug efficacy in animal models of stroke. In 50 patients diagnosed with acute ischemic stroke (<24-hour duration) within the middle cerebral artery territory, lesion volume was measured by diffusion-weighted imaging. Thirty-four patients also had volumes measured by T2-weighted imaging chronically (median time, 7.5 weeks; mean, 15.9 weeks). Clinical severity was measured by the National Institutes of Health Stroke Scale Score and the Barthel index. Acute lesion volumes correlated with the acute stroke scale score (r = 0.56), the chronic stroke scale score (r = 0.63), and chronic lesion volumes (r = 0.84). Chronic volumes correlated with the chronic stroke scale score (r = 0.86) and the Barthel index (r = -0.60). When only cortically based lesions were considered, the correlations relating acute lesion volume measured by diffusion-weighted imaging (r = 0.61) and chronic lesion volume measured by T2-weighted imaging (r = 0.90) to the chronic stroke scale score were higher. These results provide evidence that lesion volumes determined by diffusion-weighted imaging acutely may be predictive of clinical severity and outcome, and may support a role for diffusion-weighted imaging in the assessment of acute stroke therapies in clinical trials.

Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke.

Diffusion-weighted MRI can rapidly detect acute cerebral ischemic injury as hyperintense signal changes, reflecting a decline in the apparent diffusion coefficient (ADC) of water through brain parenchyma, whereas ADC is elevated in the chronic stage because of increased extracellular water content. To determine the time course of these ADC changes, we analyzed 157 diffusion-weighted MRI studies performed at varying time points from the initial ischemic event from 101 patients. Data were expressed as the relative ADC (rADC), the ratio of lesion to control regions of interest. We observed two phases in the time course of rADC changes in acute human stroke: a significant (p < 0.005) reduction in rADC lasting for at least 96 hours from stroke onset (mean, 58.3% of control; SEM, 1.47) and an increasing trend from reduction to pseudonormalization to elevation of rADC values at later subacute to chronic time points (> or = 7 days). We suggest that the persistent reduction of rADC within the first four days may reflect ongoing or progressive cytotoxic edema to a greater degree than extracellular edema and cell lysis.

STAR MR angiography for rapid detection of vascular abnormalities in patients with acute cerebrovascular disease.

BACKGROUND AND PURPOSE: We undertook to investigate the usefulness of signal targeting with alternating radiofrequency magnetic resonance angiography (STAR MRA) in the diagnosis of acute cerebrovascular disease. The potential advantage of the technique is that angiographic images can be acquired in less than 1 minute. METHODS: We studied 19 patients (11 men and 8 women, ranging in age from 36 to 84 years [mean age, 66 years]) presenting with signs and symptoms of acute stroke. Patients underwent STAR MRA and three-dimensional fast imaging with steady-state precession (3D FISP) MRA. The MRAs were analyzed as to image quality and vascular abnormalities in the vascular territory of stroke as defined by diffusion-weighted imaging abnormalities and compared using a Wilcoxon signed-rank test. RESULTS: STAR MRAs had slightly inferior image quality compared with 3D FISP MRA (P < .05). STAR MRA and 3D FISP MRA agreed in 18 of 19 cases regarding vascular abnormalities in the territory of the infarct (occlusion, n = 8; stenosis, n = 4; no abnormality, n = 6). In one patient, the techniques disagreed, when 3D FISP MRA was normal and STAR MRA demonstrated a vessel occlusion in the vascular territory of a stroke as defined by diffusion-weighted imaging abnormalities (P > .05). CONCLUSIONS: Despite slightly inferior image quality compared with 3D FISP MRA, STAR MRA is comparable with 3D FISP MRA in depicting abnormalities in the proximal parts of the cerebral arteries corresponding to ischemic regions on diffusion-weighted imaging, in a strikingly shorter acquisition time. Further studies are necessary to confirm that the smaller branches are better shown by using longer inversion times.

Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging.

We aimed to determine the frequency and time course of the enlargement of ischemic cerebral lesions following human stroke and to study the effect of the state of perfusion on lesion enlargement. Acute lesion volumes were measured on diffusion-weighted magnetic resonance images and compared with lesion volumes measured on T2-weighted images at 7 days or later. Forty-four measurements were performed between 2 and 53 hours after stroke onset in 28 patients. Thirteen patients also had magnetic resonance perfusion imaging performed. In 12 (43%) of 28 patients the initial lesion volume increased by 20% or more. The number of studies showing enlargement of the ischemic lesion volume ranged from 12 (43%) of 28 at or after 2 hours to 10 (38%) of 26 at or after 6 hours, 5 (33%) of 15 at or after 24 hours, and 2 (33%) of 6 at or after 48 hours. In 7 of the 10 patients in whom the hypoperfusion volume acutely exceeded the volume of the abnormality on diffusion-weighted images, lesion volume increased by 20% or more. This study provided evidence that substantial enlargement of human cerebral ischemic lesion volumes can occur beyond the first 6, 12, or 24 hours after onset. A mismatch acutely between the region of hypoperfusion (larger) and the region of diffusion abnormality (smaller) may be predictive of ischemic lesion enlargement.

Comparison of EPISTAR and T2*-weighted gadolinium-enhanced perfusion imaging in patients with acute cerebral ischemia.

PURPOSE: To compare echo-planar imaging with signal targeting and alternating radiofrequency (EPISTAR), an arterial spin-labeling technique, to a T2*-weighted gadolinium-enhanced (T2*-WGE) MR perfusion technique for the evaluation of acute cerebrovascular disease. METHOD: Twenty-one EPISTAR and T2*-WGE perfusion studies were performed on 18 patients with the clinical diagnosis of acute stroke (12 men, 6 women, age range 34 to 89 years, mean age 68 years). For qualitative analysis, perfusion studies of both techniques were grouped into categories (hyperperfusion, normal perfusion, delayed perfusion, or absent perfusion) and compared with a Wilcoxon signed rank test. Quantitative analysis was performed using signal intensity measurements in a region of interest that was defined by diffusion-weighted imaging abnormalities. These signal intensity measurements were compared with a mirror region in the contralateral unaffected hemisphere. Signal intensity ratios (infarcted region versus the unaffected contralateral region) were calculated and compared using a paired t test. RESULTS: Qualitative analysis demonstrated agreement between the two techniques in 17 of 21 studies (hyperfusion, n = 3 patients; normal perfusion, n = 3; delayed perfusion, n = 4; and absent perfusion, n = 7). In four studies, the two techniques disagreed when EPISTAR demonstrated absent and T2*-WGE perfusion demonstrated delayed perfusion (p > 0.05). Quantitative analysis revealed a mean signal intensity ratio of 0.73 +/- 0.79 for the T2*-WGE perfusion technique and 0.69 +/- 0.68 for the EPISTAR technique (p > 0.05). CONCLUSION: The noninvasive EPISTAR technique can assess perfusion abnormalities similarly to the T2*-WGE perfusion technique and may provide a valuable alternative in the diagnosis of acute stroke patients. Differences between the two techniques can be explained by the applied inflow times in the EPISTAR technique.

Impact of CT on diagnosis and management of acute abdomen in patients initially treated without surgery.

OBJECTIVE: The purpose of this study was to evaluate the effect of CT on the diagnosis and management of acute abdominal pain in patients who did not undergo surgery and to determine what population of patients would profit most from CT examination. MATERIALS AND METHODS: Clinical data and CT reports of 91 patients with acute abdomen (41 men and 50 women, 22-96 years old) were analyzed retrospectively. The accuracies of clinical evaluation and CT in revealing the cause of acute abdomen were compared, and the effect of CT on patient management was assessed. Analysis included the entire population of patients and these subgroups: (1) patients who had symptoms for fewer than 24 hr versus patients who had symptoms for 24 hr or more and (2) patients who had a history of abdominal diseases versus patients who had no such history. RESULTS: Twenty-nine patients had signs or symptoms for fewer than 24 hr, and 62 patients had signs or symptoms for 24 hr or more. Fifty-nine patients had a history of abdominal disease, and 32 had no history of abdominal disease. In the entire population of patients, CT was superior to clinical evaluation for diagnosing the cause of acute abdomen (sensitivity was 90% for CT and 76% for clinical evaluation, p < .0005). Management was changed after CT in 25 patients (p < .0005). Similar differences were observed in the subgroups of patients with signs and symptoms for fewer than 24 hr, patients with signs and symptoms for 24 hr or more, and patients with no history of abdominal disease (p < .05). In the subgroup of patients with a history of abdominal disease, the differences between clinical evaluation and CT were not statistically significant. CONCLUSION: CT is an excellent examination technique for patients with acute abdomen, regardless of the duration of signs and symptoms. CT is particularly useful in defining the cause and therapeutic strategy in patients with acute abdomen who have no history of abdominal disease.

Prefrontal cortex fMRI signal changes are correlated with working memory load.

We investigated whether a nonspatial working memory (WM) task would activate dorsolateral prefrontal cortex (DLPFC) and whether activation would be correlated with WM load. Using functional magnetic resonance imaging we measured regional brain signal changes in 12 normal subjects performing a continuous performance, choice reaction time task that requires WM. A high WM load condition was compared with a non-WM choice reaction time control condition (WM effect) and a low WM load condition (load effect). Significant changes in signal intensity occurred in the DLPFC, frontal motor regions and the intraparietal sulcus (IPS) in both comparisons. These findings support the role of DLPFC and IPS in WM and suggest that signal changes in DLPFC correlate with WM load.