Lisa Ehrlich

Clinical investigation: lungObserver variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion☆

PURPOSE To quantify interobserver variation in gross tumor volume (GTV) localization using CT images for patients with non-small-cell lung carcinoma and poorly defined tumors on CT and to determine whether variability would be reduced if coregistered 2-[18F]fluoro-2-deoxy-d-glucose (FDG)-hybrid positron emission tomography (PET) with CT images were used. METHODS AND MATERIALS Prospectively, 30 patients with non-small-cell lung carcinoma had CT and FDG-hybrid PET examinations in radiation treatment position on the same day. Images were coregistered using eight fiducial markers. Guidelines were established for contouring GTVs. Three radiation oncologists performed localization independently. The coefficient of variation was used to assess interobserver variability. RESULTS The size of the GTV defined showed great variation among observers. The mean ratios of largest to smallest GTV were 2.31 and 1.56 for CT only and for CT/FDG coregistered data, respectively. The addition of PET reduced this ratio in 23 of 30 cases and increased it in 7. The mean coefficient of variation for GTV based on the combined modalities was significantly smaller (p < 0.01) than that for CT data only. CONCLUSIONS High observer variability in CT-based definition of the GTV can occur. A more consistent definition of the GTV can often be obtained if coregistered FDG-hybrid PET images are used.

Simple Visual Analysis of Brain Perfusion on HMPAO SPECT Predicts Early Outcome in Acute Stroke

BACKGROUND AND PURPOSE Single-photon emission computed tomography (SPECT) is used in patients with acute stroke but as yet is of controversial value. We investigated an association of brain perfusion changes in stroke patients with stroke severity, volume of brain damage, and recovery. METHODS Consecutive patients with hemispheric stroke were studied prospectively with serial neurological examinations using the Canadian Neurological Scale (CNS), CT. and 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT. Visual SPECT patterns of brain perfusion (normal, high, mixed, low, and absent) were correlated with the severity of stroke, lesion volume, and short-term outcome. RESULTS SPECT studies were performed in a total of 458 consecutive acute stroke patients within 2 weeks after the onset (mean time, 5 days; range, 1 to 12 days). SPECT perfusion patterns correlated with stroke severity (CNS score) during the first 2 weeks (P < .001). Focal absence of brain perfusion on SPECT was associated with the largest volume of brain damage: 104 +/- 84 mL (P < .0001). SPECT perfusion patterns predicted the shortterm outcome: 97% of patients with normal and increased HMPAO uptake made good recovery, 52% of those with decreased perfusion had moderate stroke, and 62% of patients with absent patterns fared badly. In a multiple logistic regression model, admission CNS scores had the strongest predictive value (P = .0001). SPECT had its own prognostic value independent of clinical judgment (P = .03). SPECT statistically improved predictive power of the CNS score (+1% receiver operating characteristic curve area, [X2]2 = 20, P < .001) because of distinction between focal decrease or absence of brain perfusion in patients studied within the first 72 hours of stroke. CONCLUSIONS Visual brain perfusion patterns correlate with the extent, severity, and short-term outcome of hemispheric stroke. HMPAO SPECT may improve the prognostic value of clinical examination if performed during the first 72 hours of stroke.

Sentinel lymph node in vulvar cancer

The aim of the study was to assess the feasibility, efficacy, and accuracy of the sentinel lymph node (SLN) procedure in vulvar cancer.

Noninvasive assessment of intracranial perfusion in acute cerebral ischemia.

Single‐photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) may help to determine a target group of patients w1th maximum therapeutiC response for tissue rescue after acute stroke. As previously described, the cerebral perfusion mdex represents a combination of these techniques, and is calculated by multiplying assigned values for TCD and SPECT perfusion patterns. The three grades of cerebral perfusion index (1–5, 6–12, 15–20) may predict short‐term outcome if the index is based on SPECT and TCD performed w1thin the first 6 hours after stroke. A total of 30 consecutive patients were studied (18 with middle cerebral artery stroke and 12 with transient ischemic attack or minor stroke) Neurological deficit was scored using the Canadian Neurological Scale. SPECT and TCD were performed 4 ± 2 hours after the onset. Forty‐five minutes were required to perform both tests, evaluate the results, and calculate the cerebral perfusion index. The mean score ( ± standard deviation) of the neurological deficit on admission was 84 ± 20 in patients with transient ischemic attack/minor stroke and 54 ± 33 in patients with stroke (p < 0 009) The volume of 1schemic lesion was measured on computed tomography scans performed more than 3 days after the ictus. Patients with transient ischemic attack/minor stroke had lesion volumes of 8 ± 7 cm3 compared to 72 ± 26 cm3 for those with stroke (p < 0.0001). The mean cerebral perfusion index in the transient ischemic attack group was 18 ± 4, while in the stroke group it was 4 ± 1 (p < 0.0001 ). Clinical examination on admission correctly predicted a reversible neurological deficit in 9 of 12 patients in the transient ischemic attack group and the irreversibility of brain damage in 14 of 18 patients in the stroke group. With the three‐grades scale, cerebral perfusion index correctly identified 10 transient ischemic attacks and 17 strokes. Noninvasive diagnosis of intracranial perfusion abnormalities using SPECT and TCD correlates with the clinical outcome and the volume of brain damage, and therefore may improve the accuracy of prognosis in the hyperacute phase of cerebral ischemia. Cerebral perfusion index is a fast and qualitative scoring system that may be used for early differentiation of transient ischemic attacks, minor strokes, and strokes durmg the first 6 hours of cerebral ischemia.

Cerebral perfusion index: a new marker for clinical outcome in acute stroke.

Single‐photon emission computed tomography (SPECT) and transcranial Doppler (TCD) ultrasound are of good prognostic value in acute stroke, and combined they may be an accurate way to determine a target group of patients with maximum therapeutic response. Seventy consecutive patients were studied (42 with middle cerebral artery strokes, 18 with transient ischemic attacks [TIAs]; 10 were excluded due to failure of insonation). Two SPECT studies were performed at 2.1 ± 1.2 and 13.8 ± 3.1 days after onset. Serial TCD studies were done at 10 hours and at the time of the SPECT studies. Neurological deficit was scored on admission and 2 weeks later (using the Canadian Neurological Scale). Cerebral perfusion index (CPI) was derived by multiplying the values for TCD and SPECT patterns. Positive correlation was obtained in all 16 patients in whom cerebral angiography was performed within the first 3 days after onset. The occlusive TCD pattern and absence of perfusion on SPECT were common in the stroke group (19/42 patients) and were never seen in those with TIAs. A normal TCD pattern and normal perfusion on SPECT were more common in the patients with TIAs (9/18 vs 8/42, p = 0.02; 5/10 vs 1/40, p = 0.0003). The occlusive TCD and SPECT patterns were associated with the highest mean infarction volume (147 ± 87 vs 19 ± 21, p < 0.0001) and all nonocclusive TCD and SPECT patterns were associated with the better short‐term outcome (43.2 ± 33.9 vs 92.4 ± 20.2, p < 0.0001). A tendency for hyperfixation of the tracer to be more common in cardioembolic stroke was found. The three grades of the initial CPI (1–5, 6–12, 15–20) were found to predict different degrees of short‐term outcome (good, medium, and poor). The TCD and SPECT combination (CPI) may prove to be a safe, fast, and reliable noninvasive substitute for angiography.

Breast metastasis by medullary thyroid carcinoma detected by FDG positron emission tomography.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer comprising 5% to 8% of thyroid neoplasms. In contrast to common thyroid tumors, this tumor originates from the calcitonin-producing C cells. Regional metastases to cervical lymph nodes occur early in the disease, whereas distant metastasis occurs late. Common metastatic sites include the liver, bone, brain, and adrenal medulla. We present a case of MTC metastatic to the breast. We report on this case for the following reasons: (1) metastasis to the breast is an extremely rare occurrence and could be easily confused clinically and pathologically with a primary breast neoplasm and (2) this is the first reported case of detection of breast metastasis by an MTC using FDG ((18)F-fluoro-2-deoxy-D-glucose) positron emission tomography with an accompanying histologic description.

Clinical Significance of Increased Uptake of HMPAO on Brain SPECT Scans in Acute Stroke

Single‐photon emission computed tomography (SPECT) with 99mtechnetium‐hexamethylpropylamineoxirne (HMPAO) non‐invasively shows brain perfusion in patients after acute stroke. However, the clinical significance of the increased HMPAO uptake remains unclear. In this study, consecutive patients with hemispheric hemorrhagic and ischemic stroke admitted to the hospital were evaluated prospectively. The increased uptake of HMPAO was determined by visual analysis of SPECT images. The pathogenic mechanism of ischemic stroke was determined using the clinical and computed tomography (CT) criteria including the Toronto Embolic Scale. Of the 500 consecutive patients with acute hemispheric stroke, SPECT was performed in 458 at a mean time of 5 ± 7 days after the onset of symptoms. A strong association was found between SPECT perfusion patterns and pathogenic subtypes of stroke (p < 0.0001). Thus, in 95% of patients with intracerebral hemorrhage the focal absence of perfusion was found, and 26% of lacunar infarctions presented with a normal SPECT appearance. The mean volume of lacunar lesions that did not produce significant abnormalities on SPECT was 2.5 ± 1.2 ml. Increased HMPAO uptake was associated with a cardioembolic mechanism of stroke: High and mixed perfusion patterns were present subacutely in 29% of patients with cardioembolic stroke, compared to 15% of patients with other types of ischemic stroke (p ≤ 0.0006). The increased uptake of HMPAO on SPECT as determined by visual analysis is associated with a cardioembolic mechanism of cerebral ischemia, which could be explained by glutathione‐mediated trapping of the tracer during reperfusion and later in newly developed granulation tissue. HMPAO‐SPECT may help in early management decisions since it indicates stroke pathogenesis and evolution.

Differentiating between visual hallucination-free dementia with Lewy bodies and corticobasal syndrome on the basis of neuropsychology and perfusion single-photon emission computed tomography.

IntroductionDementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities.MethodsProspectively recruited case–control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them.ResultsThe Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer’s disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups.ConclusionsReduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.

Old wine in new bottles: validating the clinical utility of SPECT in predicting cognitive performance in mild traumatic brain injury.

The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis.

Radiomics analysis at PET/CT contributes to prognosis of recurrence and survival in lung cancer treated with stereotactic body radiotherapy

We sought to quantify contribution of radiomics and SUVmax at PET/CT to predict clinical outcome in lung cancer patients treated with stereotactic body radiotherapy (SBRT). 150 patients with 172 lung cancers, who underwent SBRT were retrospectively included. Radiomics were applied on PET/CT. Principal components (PC) for 42 CT and PET-derived features were examined to determine which ones accounted for most of variability. Survival analysis quantified ability of radiomics and SUVmax to predict outcome. PCs including homogeneity, size, maximum intensity, mean and median gray level, standard deviation, entropy, kurtosis, skewness, morphology and asymmetry were included in prediction models for regional control (RC) [PC4-HR:0.38, p = 0.02], distant control (DC) [PC4-HR:0.51, p = 0.02 and PC1-HR:1.12, p = 0.01], recurrence free probability (RFP) [PC1-HR:1.08, p = 0.04], disease specific survival (DSS) [PC2-HR:1.34, p = 0.03 and PC3-HR:0.64, p = 0.02] and overall survival (OS) [PC4-HR:0.45, p = 0.004 and PC3-HR:0.74, p = 0.02]. In combined analysis with SUVmax, PC1 lost predictive ability over SUVmax for RFP [HR:1.1, p = 0.04] and DC [HR:1.13, p = 0.002], while PC4 remained predictive of DC independent of SUVmax [HR:0.5, p = 0.02]. Radiomics remained the only predictors of OS, DSS and RC. Neither SUVmax nor radiomics predicted recurrence free survival. Radiomics on PET/CT provided complementary information for prediction of control and survival in SBRT-treated lung cancer patients.