Jeff Thiel

Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate

We describe the development of fetal brain lesions after Zika virus (ZIKV) inoculation in a pregnant pigtail macaque. Periventricular lesions developed within 10 d and evolved asymmetrically in the occipital–parietal lobes. Fetal autopsy revealed ZIKV in the brain and significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury. Our observation of ZIKV-associated fetal brain lesions in a nonhuman primate provides a model for therapeutic evaluation.

First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones

PURPOSE Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. MATERIALS AND METHODS Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. RESULTS Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. CONCLUSIONS Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure.

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Stone-mode ultrasound for determining renal stone size

PURPOSE The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo. MATERIALS AND METHODS Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S-mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency. Stone and shadow width were compared with a recent CT scan and, in 5 subjects with 18 stones, S-mode was compared with a clinical US system. RESULTS Overall, 84% of stones identified on CT were detected on S-mode and 66% of these shadowed. Seventy-three percent of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT. A posterior acoustic shadow was present in 89% of stones over 5 mm versus 53% of stones under 5 mm. S-mode visualized 78% of stones, versus 61% for the clinical system. S-mode stone and shadow measurements differed from CT by 1.6 ± 1.0 mm and 0.8 ± 0.6 mm, respectively, compared with 2.0 ± 1.5 mm and 1.6 ± 1.0 mm for the clinical system. CONCLUSIONS S-mode offers improved visualization and sizing of renal stones. With S-mode, sizing of the stone itself and the posterior acoustic shadow were similarly accurate. Stones that do not shadow are most likely <5 mm and small enough to pass spontaneously.

Impact of Image Orientation on Measurements of Thyroid Nodule Stiffness Using Shear Wave Elastography

To assess the effect of orientation on the stiffness measurement by shear wave elastography (SWE) within a thyroid nodule.

Variability in Stiffness Assessment in a Thyroid Nodule Using Shear Wave Imaging.

Purpose The aim of the study was to assess intrareader and interreader variability in placing a region of interest in the elastography color map in the thyroid nodule. Method and Materials After institutional review board approval, elastograms were obtained by shear wave elastography from 38 individuals, with a total of 60 thyroid nodules. Two readers reviewed all images while blinded to the cytopathology or final histopathology results and to each others measurements. For each image, readers first performed a qualitative assessment and recorded presence of stiff region(s) and number of stiff regions. Then, they placed a 3-mm circular region of interest on the stiffest region to quantify the mean and maximum stiffness in kilopascals. Intrareader and interreader agreement was summarized for categorical variables using Cohen &kgr; and for continuous variables using the concordance correlation coefficient (CCC) and coefficient of variation. Results There was good overall intrareader and interreader agreement for the presence of stiff regions and number of stiff regions after classifying them as 0, 1, and greater than 1 regions (&kgr; = 0.78–0.81 and 0.74–0.79, respectively). There was also good overall agreement for the the following quantitative measurements: mean kPa (CCC = 0.97 and 0.93) and max kPa (CCC = 0.97 and 0.93). The intrareader and interreader coefficient of variation was 13% and 21% for mean kPa and 14% and 21% for max kPa. Conclusions There can be differences in measurement of stiffness by 2 different operators in softer nodules with shear wave imaging because of the lack of brighter areas on the color elastograms. A standardized technique is necessary to be able to compare results from 1 study to the next.

Kidney stone specific ultrasound imaging of human subjects

Sensitivity and specificity data show users have more difficulty in identifying stones accurately in B-mode ultrasound than x-ray CT. Our goal was to evaluate the signal to noise (SNR) of a new stone specific imaging algorithm, S-mode based on Color Doppler twinkling artifact, to B-mode. Forty sets of B- and S-mode imaging data were collected from 16 subjects using a Philips HDI C5-2 imaging probe and Verasonics ultrasound system. Two ways S-mode differs from Doppler is that it filters out blood flow signal and uses reverse color write priority to add color to echogenic regions only. For both B- and S-mode raw data, we calculate SNR of the magnitude (brightness) of the stone signal compared to the second highest magnitude in the image. The mean and standard deviation of the SNR was 1.6 ± 0.7 for B-mode and 37 ± 24 for S-mode, with 1 being the stone is equally bright as, and difficult to distinguish from, background. In this human study of S-mode, stones appeared over 30 times brighter than background and ...

Artifacts in Shear Wave Elastography Images of Thyroid Nodules

The purpose of the study described here was to evaluate the presence and types of artifacts seen in color elastograms in thyroid elastography using shear wave elastography. This Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant study was approved by the ethics committee of our institution, and all patients provided written informed consent. One hundred seventy-eight patients (40 men and 138 women; mean age, 49 y; range, 19-84 y) were enrolled for a total of 241 thyroid nodules. After a short ultrasound (US) examination, SWE images were acquired at multiple levels in the nodule in transverse and longitudinal orientations. A total of 1297 images were obtained from 241 nodules for an average of 5.4 ±  2.7 (mean ± standard deviation) images per nodule. A retrospective review of all images was performed by one reviewer experienced in thyroid elastography. Two hundred eighty images (21.6%) were rated as good quality, and 112 (8.6%) were rated as moderate quality without artifacts. A total of 905 (69.8%) images had some artifact present, though most of these images (73.4%) were still interpretable. Two hundred forty-one images (18.6% of all images) were considered uninterpretable because of artifact. The most common types of artifacts were due to operator error (44.6% of all images), primarily compression (36.5% of all images). Other artifacts seen were due to anatomy (presence of carotid pulsation or adjacent to thyroid or location in isthmus, 11% of all images), nodule characteristics (cystic and calcified nodules or large nodules with lack of penetration, 17% of all images) and other artifacts that could not be explained by the prior mentioned causes (13% of all images). Our study indicates that artifacts are common in elastography images. Operator error was the most common type of artifact we saw. This should be easily correctable by adequate knowledge and recognition with subsequent correction of the artifacts.

Preclinical safety and effectiveness of a longer beam and burst duration for ultrasonic repositioning of urinary stones

In the first-in-human trial of ultrasonic propulsion, subjects passed collections of residual stone fragments after repositioning with a C5-2 probe. Here, effectiveness and safety in moving multiple fragments is compared between the C5-2 and a custom SC-50 probe that produces a longer beam and burst duration.

Preliminary results of the feasibility to reposition kidney stones with ultrasound in humans

Preliminary investigational use of ultrasound to reposition human kidney stones is reported. The three study arms include: de novo stones, post-lithotripsy fragments, and large stones within the preoperative setting. A pain questionnaire is completed immediately prior to and following propulsion. A maximum of 40 push attempts are administered. Movement is classified as no motion, movement with rollback or jiggle, or movement to a new location. Seven subjects have been enrolled and undergone ultrasonic propulsion to date. Stones were identified, targeted, and moved in all subjects. Subjects who did not have significant movement were in the de novo arm. None of the subjects reported pain associated with the treatment. One subject in the post-lithotripsy arm passed two small stones immediately following treatment corresponding to the two stones displaced from the interpolar region. Three post-lithotripsy subjects reported passage of multiple small fragments within two weeks of treatment. In four subjects, ul...